scholarly journals Five-Year Longitudinal Assessment (2008 to 2012) of E-101 Solution Activity against Clinical Target and Antimicrobial-Resistant Pathogens

2014 ◽  
Vol 58 (8) ◽  
pp. 4911-4914 ◽  
Author(s):  
Gerald A. Denys ◽  
Chris M. Pillar ◽  
Daniel F. Sahm ◽  
Peter O'Hanley ◽  
Jackson T. Stephens

ABSTRACTThis study summarizes the topical E-101 solution susceptibility testing results for 760 Gram-positive and Gram-negative target pathogens collected from 75 U.S. sites between 2008 and 2012 and 103 ESKAPE pathogens. E-101 solution maintained potent activity against all bacterial species studied for each year tested, with MICs ranging from <0.008 to 0.25 μg porcine myeloperoxidase (pMPO)/ml. These results confirm that E-101 solution retains its potent broad-spectrum activity against U.S. clinical isolates and organisms with challenging resistance phenotypes.

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S419-S420 ◽  
Author(s):  
Denis Daigle ◽  
Jodie Hamrick ◽  
Cassandra Chatwin ◽  
Natalia Kurepina ◽  
Barry N Kreiswirth ◽  
...  

Abstract Background VNRX-5133 is a cyclic boronate β-lactamase inhibitor (BLI) currently in clinical development with cefepime to treat multidrug-resistant (MDR) infections caused by ESBL- and carbapenemase-producing Enterobacteriaceae (ENT) and P. aeruginosa (PSA). VNRX-5133 has direct inhibitory activity against serine-active site β-lactamases (Ser-BL) and emerging VIM/NDM metallo-β-lactamases (MBL). We show herein that cefepime/VNRX-5133 is highly active against MDR-K. pneumoniae and P. aeruginosa clinical isolates producing BL-variants evolved during therapy that compromise activity of ceftazidime/avibactam and ceftolozane/tazobactam. Methods Susceptibility testing was performed according to CLSI methods with cefepime, ceftolozane, and ceftazidime alone or in combination with VNRX-5133, avibactam, or tazobactam, respectively, fixed at 4 mg/L. Five clinical isolates of K. pneumoniae producing KPC variants impacting ceftazidime/avibactam and five clinical isolates of P. aeruginosa producing Pseudomonas-derived cephalosporinase variants impacting ceftolozane/tazobactam activity were collected in 2016 and 2017, respectively, from United States and Spanish hospitals. All other clinical isolates of Enterobacteriaceae and P. aeruginosa (n = 40) were collected in 2016. Results Cefepime/VNRX-5133 was highly active against five ceftazidime/avibactam-resistant K. pneumoniae clinical isolates producing KPC variants with MIC ranging from 0.5 to 4 mg/L relative to ceftazidime/avibactam MIC range of 16 to &gt;128 mg/L. Cefepime/VNRX-5133 was also active against all five clinical isolates of ceftolozane/tazobactam-resistant P. aeruginosa, where 4/5 isolates had MIC of 4–8 mg/L relative to ceftolozane/tazobactam MIC range of 32–128 mg/L. The elevated cefepime/VNRX-5133 MIC (16 mg/L) in the remaining P. aeruginosa isolate was not due to the PDC-221 variant, as an engineered strain of P. aeruginosa producing this enzyme had a cefepime/VNRX-5133 MIC of 1 mg/L. Conclusion VNRX-5133 is a potent BLI possessing a unique broad spectrum of activity, including Class A, C, and D Ser-BLs, clinically evolving variants of Ser-BLs (e.g., KPC, PDC) and emerging VIM/NDM-type MBLs. Cefepime/VNRX-5133 is highly active against emerging multidrug-resistant Enterobacteriaceae and P. aeruginosa. Disclosures D. Daigle, VenatoRx Pharmaceuticals Inc.: Employee and Shareholder, Salary. J. Hamrick, VenatoRx Pharmaceuticals Inc.: Employee, Salary. C. Chatwin, VenatoRx Pharmaceuticals Inc.: Employee, Salary. N. Kurepina, VenatoRx Pharmaceuticals Inc.: Research Contractor, Research support. B. N. Kreiswirth, VenatoRx Pharmaceuticals Inc.: Research Contractor, Research support. R. K. Shields, VenatoRx Pharmaceuticals Inc.: Research Contractor, Research support. A. Oliver, VenatoRx Pharmaceuticals Inc.: Research Contractor, Research support. C. J. Clancy, VenatoRx Pharmaceuticals Inc.: Research Contractor, Research support. M. H. Nguyen, VenatoRx Pharmaceuticals Inc.: Research Contractor, Research support. D. Pevear, VenatoRx Pharmaceuticals Inc.: Employee, Salary. L. Xerri, VenatoRx Pharmaceuticals Inc.: Employee and Shareholder, Salary.


2021 ◽  
Vol 3 (1) ◽  
pp. 047-055
Author(s):  
Pimpliskar Mukesh ◽  
SoumyaGounder ◽  
Rahul Jadhav

Background: Handwashing is underlined as the absolute most significant measure to forestall cross-transmission of small-scale life forms and consequently to forestall nosocomial contaminations. Be that as it may, under routine emergency clinic practice consistent with this measure is still unsatisfactorily low, under half in many investigations distributed in the previous 20 years. This consistent finding is stressing because ongoing investigations have demonstrated that this degree of consistency won't decrease the danger of transmission of multi- medicate safe microscopic organisms in the emergency clinics. Results: In the present investigation effect of marketed hand washed namely Lifebuoy, Dettol and Savlon were tested on bacteria E. coli, S.aureus, S.pyogen, Klebshiella and, fungi Candida albicans. All the handwash at concentrated level found to be effective but only Dettol hand wash could give inhibitory action at 25ug/ml against Klebshiella while others at50ug/ml. Conclusions: Soapex and Dettol soap had broad spectrum activity as it inhibited the growth of Gram positive (Streptococcus pyogen) and Gram-negative (Escherichia coli). Liquid handwash such as Lifebuoy,Dettol and Savlon showed broad spectrum activity on both Gram-positive and Gram negative test microorganisms.


2020 ◽  
Vol 65 (1) ◽  
pp. e01527-20
Author(s):  
Karen Marie Thyssen Astvad ◽  
Karin Meinike Jørgensen ◽  
Rasmus Krøger Hare ◽  
Raluca Datcu ◽  
Maiken Cavling Arendrup

ABSTRACTOlorofim is a novel antifungal drug in phase 2 trials. It has shown promising in vitro activity against various molds, except for Mucorales. Initially, we observed a broad range of EUCAST MICs for Aspergillus fumigatus. Here, we explored the MIC variability in more detail and prospectively investigated the susceptibility of contemporary clinical mold isolates, as population data are needed for future epidemiological cutoff (ECOFF) settings. Fifteen A. fumigatus isolates previously found with low/medium/high MICs (≤0.002 to 0.25 mg/liter) were tested repeatedly and EUCAST MICs read in a blinded fashion by three observers. pyrE, encoding the olorofim target enzyme dihydroorotate dehydrogenase (DHODH), was sequenced. A total of 1,423 mold isolates (10 Aspergillus species complexes [including 1,032 A. fumigatus isolates] and 105 other mold/dermatophyte isolates) were examined. Olorofim susceptibility (modal MIC, MIC50, MIC90, and wild-type upper limits [WT-ULs] [species complexes with ≥15 isolates]) was determined and compared to that of four comparators. MICs (mg/liter) were within two 2-fold dilutions (0.016 to 0.03) for 473/476 determinations. The MIC range spanned four dilutions (0.008 to 0.06). No significant pyrE mutations were found. Modal MIC/WT-UL97.5 (mg/liter) values were 0.03/0.06 (A. terreus and A. flavus), 0.06/0.125 (A. fumigatus and Trichophyton rubrum), and 0.06/0.25 (A. niger and A. nidulans). The MIC range for Scedosporium spp. was 0.008 to 0.25. Olorofim susceptibility was similar for azole-resistant and -susceptible isolates of A. fumigatus but reduced for A. montevidensis and A. chevalieri (MICs of >1). With experience, olorofim susceptibility testing is robust. The testing of isolates from our center showed uniform and broad-spectrum activity. Single-center WT-ULs are suggested.


2011 ◽  
Vol 55 (5) ◽  
pp. 2398-2402 ◽  
Author(s):  
Chau Minh Tran ◽  
Kaori Tanaka ◽  
Yuka Yamagishi ◽  
Takatsugu Goto ◽  
Hiroshige Mikamo ◽  
...  

ABSTRACTWe evaluated thein vitroantianaerobic activity of razupenem (SMP-601, PTZ601), a new parenterally administered carbapenem, against 70 reference strains and 323 clinical isolates. Razupenem exhibited broad-spectrum activity against anaerobes, inhibiting most of the reference strains when used at a concentration of ≤1 μg/ml. Furthermore, it exhibited strong activity, comparable to those of other carbapenems (meropenem and doripenem), against clinically isolated non-fragilis Bacteroidesspp. (MIC90s of 2 μg/ml), with MIC90values of 0.06, 0.03, and 0.5 μg/ml againstPrevotellaspp.,Porphyromonasspp., andFusobacteriumspp., respectively. Clinical isolates of anaerobic Gram-positive cocci,Eggerthellaspp., andClostridiumspp. were highly susceptible to razupenem (MIC90s, 0.03 to 1 μg/ml).


2009 ◽  
Vol 53 (8) ◽  
pp. 3552-3560 ◽  
Author(s):  
Wolfgang Haas ◽  
Chris M. Pillar ◽  
Gary E. Zurenko ◽  
Jacqueline C. Lee ◽  
Lynne S. Brunner ◽  
...  

ABSTRACT The antibacterial spectrum of besifloxacin, a novel fluoroquinolone recently approved for treatment of ocular infections, was studied using 2,690 clinical isolates representing 40 species. Overall, besifloxacin was the most potent agent tested against gram-positive pathogens and anaerobes and was generally equivalent to comparator fluoroquinolones in activity against most gram-negative pathogens. Besifloxacin demonstrated potent, broad-spectrum activity, which was particularly notable against gram-positive and gram-negative isolates that were resistant to other fluoroquinolones and classes of antibacterial agents.


PLoS ONE ◽  
2020 ◽  
Vol 15 (3) ◽  
pp. e0231231
Author(s):  
Michele S. Y. Tan ◽  
Dara Davison ◽  
Mateo I. Sanchez ◽  
Bethany M. Anderson ◽  
Stephen Howell ◽  
...  

2020 ◽  
Vol 11 (12) ◽  
pp. 1379-1385
Author(s):  
R. Kirk ◽  
A. Ratcliffe ◽  
G. Noonan ◽  
M. Uosis-Martin ◽  
D. Lyth ◽  
...  

We disclose the discovery of REDX07965, a novel tricyclic topoisomerase inhibitor (NTTI) which has broad spectrum activity, favourable in vitro pharmacokinetic properties and selectivity versus human topoisomerase II.


2018 ◽  
Vol 152 ◽  
pp. 318-328 ◽  
Author(s):  
Moustafa ElAwamy ◽  
Haroon Mohammad ◽  
Abdelrahman Hussien ◽  
Nader S. Abutaleb ◽  
Mohamed Hagras ◽  
...  

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