Search results for "teicoplanin"
showing 10 items of 11 documents
Complex Regulatory Networks Governing Production of the Glycopeptide A40926
2018
Glycopeptides (GPAs) are an important class of antibiotics, with vancomycin and teicoplanin being used in the last 40 years as drugs of last resort to treat infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. A few new GPAs have since reached the market. One of them is dalbavancin, a derivative of A40926 produced by the actinomycete Nonomuraea sp. ATCC 39727, recently classified as N. gerenzanensis. This review summarizes what we currently know on the multilevel regulatory processes governing production of the glycopeptide A40926 and the different approaches used to increase antibiotic yields. Some nutrients, e.g., valine, l-glutamine and mal…
A Two-Component regulatory system with opposite effects on glycopeptide antibiotic biosynthesis and resistance
2020
AbstractThe glycopeptide A40926, produced by the actinomycete Nonomuraea gerenzanensis, is the precursor of dalbavancin, a second-generation glycopeptide antibiotic approved for clinical use in the USA and Europe in 2014 and 2015, respectively. The final product of the biosynthetic pathway is an O-acetylated form of A40926 (acA40926). Glycopeptide biosynthesis in N. gerenzanensis is dependent upon the dbv gene cluster that encodes, in addition to the two essential positive regulators Dbv3 and Dbv4, the putative members of a two-component signal transduction system, specifically the response regulator Dbv6 and the sensor kinase Dbv22. The aim of this work was to assign a role to these two ge…
Efficacy and safety of dalbavancin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and other infections in a real-li…
2020
Objectives: We evaluated the efficacy and safety of dalbavancin in ABSSSI and ‘other sites’ infections’ (OTA). Methods: Observational study involving 11 Italian hospitals including patients that received ≥1 dose of dalbavancin in 2016–2019. The outcome was end-of-treatment efficacy and safety in ABSSSI and OTA in a real-life setting. Results: 206 patients enrolled (males 50%, median age 62 [IQR 50–76] years), 60.2% ABSSSI, 39.8% OTA. 69.7% ABSSSI vs 90.7% OTA (p = 0.003) and 46.3% ABSSSI vs 37.2% OTA (p = 0.786) received previous and concomitant antibiotics, respectively. 82.5% reached clinical cure. Eleven (5.4%) patients had non-serious adverse events (AE). OTA patients showed longer hosp…
Extended-spectrum beta-lactamase-producing and carbapenemase-producing Enterobacter cloacae ventriculitis successfully treated with intraventricular …
2014
SummaryWe present a case of post-neurosurgical ventriculitis caused by carbapenemase-producing Enterobacter cloacae successfully treated with intraventricular colistin. Enterobacter spp are intrinsically resistant to aminopenicillins, cefazolin, and cefoxitin due to the production of constitutive chromosomal AmpC beta-lactamases. Moreover, extended-spectrum beta-lactamase-producing Enterobacter spp have been identified in the USA and Europe, and carbapenems are considered the drug of choice in these cases. Our isolate was sensitive only to fosfomycin, tigecycline, and colistin, and 6 days of intravenous colistin had failed to eradicate the infection. This case provides clinical evidence to …
Phosphate-controlled regulator for the biosynthesis of the dalbavancin precursor A40926
2007
ABSTRACT The actinomycete Nonomuraea sp. strain ATCC 39727 produces the glycopeptide A40926, the precursor of the novel antibiotic dalbavancin. Previous studies have shown that phosphate limitation results in enhanced A40926 production. The A40926 biosynthetic gene ( dbv ) cluster, which consists of 37 genes, encodes two putative regulators, Dbv3 and Dbv4, as well as the response regulator (Dbv6) and the sensor-kinase (Dbv22) of a putative two-component system. Reverse transcription-PCR (RT-PCR) and real-time RT-PCR analysis revealed that the dbv14 - dbv8 and the dbv30 - dbv35 operons, as well as dbv4 , were negatively influenced by phosphate. Dbv4 shows a putative helix-turn-helix DNA-bind…
Two master switch regulators trigger A40926 biosynthesis in Nonomuraea sp. strain ATCC 39727
2015
ABSTRACT The actinomycete Nonomuraea sp. strain ATCC 39727 produces the glycopeptide A40926, the precursor of dalbavancin. Biosynthesis of A40926 is encoded by the dbv gene cluster, which contains 37 protein-coding sequences that participate in antibiotic biosynthesis, regulation, immunity, and export. In addition to the positive regulatory protein Dbv4, the A40926-biosynthetic gene cluster encodes two additional putative regulators, Dbv3 and Dbv6. Independent mutations in these genes, combined with bioassays and liquid chromatography-mass spectrometry (LC-MS) analyses, demonstrated that Dbv3 and Dbv4 are both required for antibiotic production, while inactivation of dbv6 had no effect. In …
Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: Lessons from the DAL…
2014
The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The followi…
The role of dalbavancin for Gram positive infections in the COVID-19 era: state of the art and future perspectives
2021
INTRODUCTION: The COVID-19 pandemic has dramatically challenged the national health systems worldwide in the last months. Dalbavancin is a novel antibiotic with a long plasmatic half-life and simplified weekly administration regimens, thus representing a promising option for the outpatient treatment of Gram-positive infections and the early discharge of hospitalized patients. Dalbavancin is approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Many preliminary data seem to support its use in other indications, such as osteomyelitis, prosthetic joint infections, and infective endocarditis. AREAS COVERED: A search in the literature using validated keyword…
VanB-VanC1 Enterococcus gallinarum, Italy
2005
To the Editor: We report detecting a vanB determinant in Enterococcus gallinarum in poultry in Italy. High-level vanA-mediated glycopeptide resistance has been described for E. gallinarum and E. casseliflavus (1–4), and vanB-mediated vancomycin resistance has been frequently described for E. faecalis and E. faecium. However, vanB-mediated resistance in isolates of E. gallinarum has been described only in sporadic nosocomial cases of infection or colonization (5,6). In January 2005, a study of contamination by foodborne organisms in slaughtered broiler carcasses was conducted in Sicily. To detect glycopeptide-resistant enterococci (GRE), each carcass was placed in a bag with 100 mL sterile b…
dltA overexpression: A strain-independent keystone of daptomycin resistance in methicillin-resistant Staphylococcus aureus
2013
The mechanisms leading to reduced susceptibility to daptomycin (DAP) are multifactorial and have not been fully elucidated. We analysed, by sequencing and expression studies, the role of the major molecular targets (cell-envelope charge genes, dltA, mprF, cls2; cell-wall turnover and autolysis genes, sceD, atl) involved in the emergence of DAP resistance in three series of isogenic clinical methicillin-resistant Staphylococcus aureus (MRSA) in which DAP resistance emerged after a heterogeneous glycopeptide-intermediate S. aureus (hGISA) step under teicoplanin and DAP therapy. All of the isolates had different genotypes and were delta-haemolysin negative, reflecting a strain proclivity to ac…