glycopeptide antibiotic
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2022 ◽  
Vol 15 (1) ◽  
pp. 77
Author(s):  
Ilona Bereczki ◽  
Zsolt Szűcs ◽  
Gyula Batta ◽  
Tamás Milán Nagy ◽  
Eszter Ostorházi ◽  
...  

Various dimeric derivatives of the glycopeptide antibiotic teicoplanin were prepared with the aim of increasing the activity of the parent compound against glycopeptide-resistant bacteria, primarily vancomycin-resistant enterococci. Starting from teicoplanin, four covalent dimers were prepared in two orientations, using an α,ω-bis-isothiocyanate linker. Formation of a dimeric cobalt coordination complex of an N-terminal L-histidyl derivative of teicoplanin pseudoaglycone has been detected and its antibacterial activity evaluated. The Co(III)-induced dimerization of the histidyl derivative was demonstrated by DOSY experiments. Both the covalent and the complex dimeric derivatives showed high activity against VanA teicoplanin-resistant enterococci, but their activity against other tested bacterial strains did not exceed that of the monomeric compounds.


Author(s):  
Shang Jiao ◽  
Dongliang Guan ◽  
Lili Xu ◽  
Bo Liu ◽  
Weiwei Shi ◽  
...  

Fermentation ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. 140
Author(s):  
Elisa Binda ◽  
Francesca Berini ◽  
Flavia Marinelli ◽  
Adriana Bava ◽  
Fabrizio Beltrametti

Nonomuraea gerenzanensis ATCC 39727 produces the glycopeptide antibiotic A40926, which is the natural precursor of the semi-synthetic, last-resort drug dalbavancin. To reduce the cost of dalbavancin production, it is mandatory to improve the productivity of the producing strain. Here, we report that the exposure of N. gerenzanensis wild-type population to sub-inhibitory concentrations of A40926 led to the isolation of differently resistant phenotypes to which a diverse A40926 productivity was associated. The most resistant population (G, grand colonies) represented at least the 20% of the colonies growing on 2 µg/mL of A40926. It showed a stable phenotype after sub-culturing and a homogeneous profile of self-resistance to A40926 in population analysis profile (PAP) experiments. The less resistant population (P, petit) was represented by slow-growing colonies to which a lower A40926 productivity was associated. At bioreactor scale, the G variant produced twice more than the wild-type (ca. 400 mg/L A40926 versus less than 200 mg/L, respectively), paving the way for a rational strain improvement based on the selection of increasingly self-resistant colonies.


2021 ◽  
Author(s):  
Bingyu Yan ◽  
Wen Gao ◽  
Li Tian ◽  
Shuai Wang ◽  
Huijun Dong

Abstract Objective To enhance the production of A40926 by implementing a strategy of the combination of genetically engineered strain construction and medium optimization. Results The engineered strain of Nonomuraea gerenzanensis presented an increment of 30.6 percent in A40926 production compared with that of the parent strain. Subsequently, an assembling medium, which was defined as M9 medium and mainly comprised glucose, maltodextrin, soybean meal, peptone, L-valine, and other inorganic salts, was determined as the optimal medium among the tested nine media. The optimum concentration of medium components was glucose 10 g/l, maltodextrin 37.9 g/l, soybean meal 34.5 g/l, peptone 30.0 g/l, and L-valine 4.3 g/l, respectively. The optimized medium was verified experimentally, and A40926 yield increased significantly from 257 mg/l to 332 mg/l, as compared to the non-optimized medium. The strategy brought a significant increase of A40926 yield by 65.2 percent. Conclusions The engineered mutant with the genetic attributes of the co-expression of the dbv3 and dbv20 genes and the deletion of the dbv23 gene could obviously enhance the production of A40926. In addition, the optimization of medium was an effective and essential tool for the improvement of the secondary metabolites in Actinomyces.


2021 ◽  
Vol 30 (5) ◽  
pp. 390-393
Author(s):  
Nora Zenati ◽  
Charles Khouri ◽  
Carole Schwebel ◽  
Sophie Blaise

Vancomycin is a tricyclic glycopeptide antibiotic produced from Streptococcus orientalis. There is much variation in the literature with regard to the recommended dose, dilution rate and type of infusion. Given the vesicant properties of vancomycin at supratherapeutic doses (>10mg/ml), tissue damage including blistering and necrosis have been reported. We report a rare case of bilateral cutaneous necrosis induced by accidental extravasation of vancomycin when being intravenously administered. The skin surrounding the injection site was marked by the appearance of subcutaneous calcifications. The development of iatrogenic skin calcinosis has not yet been described for the extravasation of vancomycin. The mechanism underlying the calcinosis observed in our case remains unclear, but we hypothesised a form of localised calciphylaxis induced by a local triggering factor. The ulcers progressed to re-epithelialisation following necrosis debridement and local conservative treatments. Given the increased prevalence of meticillin-resistant Staphylococcus aureus, which has prompted clinicians to gradually increase vancomycin dosage, clinicians should be aware of the high risk of skin toxicity in cases of vancomycin high-dose extravasation.


Author(s):  
Oleksandr Yushchuk ◽  
Natalia M. Vior ◽  
Andres Andreo-Vidal ◽  
Francesca Berini ◽  
Christian Rückert ◽  
...  

Author(s):  
Chih-Hsun Tai ◽  
Chi-Hao Shao ◽  
Chi-Chuan Wang ◽  
Fang-Ju Lin ◽  
Jann-Tay Wang ◽  
...  

Abstract Background The concurrent use of vancomycin and piperacillin/tazobactam increases the risk of acute kidney injury (AKI) compared with vancomycin use with other anti-pseudomonal β-lactams (OAPBs). Teicoplanin is a glycopeptide antibiotic with lower nephrotoxicity than that of vancomycin. Whether the concomitant use of teicoplanin and piperacillin/tazobactam also increases the risk of AKI remains unknown. Objectives To evaluate the AKI risk between teicoplanin–piperacillin/tazobactam and teicoplanin–OAPBs. Methods This was a retrospective, propensity score-matched cohort study. Adult patients receiving teicoplanin-based combination therapy were included. OAPBs included cefepime, cefoperazone/sulbactam, ceftazidime, doripenem, imipenem/cilastatin and meropenem. Propensity score matching was performed to balance demographic and confounding factors. The primary endpoint was AKI during combination therapy. Results After propensity score matching, 954 patients (teicoplanin–piperacillin/tazobactam: teicoplanin–OAPBs, 1:3 matched, 243 pairs in total) were included for analysis. The mean age was 66.3 years in the matched cohort and 17.1% of patients had shock. Use of nephrotoxic medications (45.7% versus 48.7%) and baseline renal function (78.88 ± 31.26 versus 81.05 ± 31.53 mL/min/1.73 m2) were similar in the two groups. The median teicoplanin dose was 10.7 mg/kg in both groups. The groups did not differ significantly in terms of AKI risk (14.8% versus 14.2%, P = 0.815). However, the time to AKI appeared shorter in the teicoplanin–piperacillin/tazobactam group (4.64 ± 2.33 versus 6.29 ± 4.72 days, P = 0.039). Conclusions The combination of teicoplanin and piperacillin/tazobactam was not associated with an increased risk of AKI compared with teicoplanin and OAPBs.


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