scholarly journals Potential Synergy Activity of the Novel Ceragenin, CSA-13, against Carbapenem-ResistantAcinetobacter baumanniiStrains Isolated from Bacteremia Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Cagla Bozkurt-Guzel ◽  
Paul B. Savage ◽  
Alper Akcali ◽  
Berna Ozbek-Celik
Keyword(s):  
Antimicrobial Agents ◽  
Pharmacokinetic Parameters ◽  
The Novel ◽  
Chronic Infections ◽  
New Class ◽  
Synergistic Interactions ◽  
Carbapenem Resistant ◽  
Potential Synergy ◽  
Blood Specimens

Carbapenem-resistantAcinetobacter baumanniiis an important cause of nosocomial infections, particularly in patients in the intensive care units. As chronic infections are difficult to treat, attempts have been made to discover new antimicrobials. Ceragenins, designed to mimic the activities of antimicrobial peptides, are a new class of antimicrobial agents. In this study, the in vitro activities of CSA-13 either alone or in combination with colistin (sulphate), tobramycin, and ciprofloxacin were investigated using 60 carbapenem-resistantA. baumanniistrains isolated from bacteremia patients blood specimens. MICs and MBCs were determined by microbroth dilution technique. Combinations were assessed by using checkerboard technique. The MIC50values (mg/L) of CSA-13, colistin, tobramycin, and ciprofloxacin were 2, 1, 1.25, and 80, respectively. The MIC90(mg/L) of CSA-13 and colistin were 8 and 4. The MBCs were equal to or twice greater than those of the MICs. Synergistic interactions were mostly seen with CSA-13-colistin (55%), whereas the least synergistic interactions were observed in the CSA-13-tobramycin (35%) combination. No antagonism was observed. CSA-13 appears to be a good candidate for further investigations in the treatment ofA. baumanniiinfections. However, future studies should be performed to correlate the safety, efficacy, and pharmacokinetic parameters of this molecule.

scholarly journals 687. In vitro Activity of a New Generation Oxopyrazole Antibiotic Against Acinetobacter spp.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S312-S312
Author(s):  
Joel Goldberg ◽  
Christopher Bethel ◽  
Andrea M Hujer ◽  
Kristine Hujer ◽  
Steven Marshall ◽  
...  
Keyword(s):  
In Vitro Activity ◽  
Penicillin Binding Proteins ◽  
Hospital Acquired Infections ◽  
New Class ◽  
Carbapenem Resistant ◽  
Acinetobacter Spp ◽  
Gram Negative Organisms ◽  
New Generation ◽  
Hospital Acquired

Abstract Background Acinetobacter spp. resistant to common antibiotics have become a worrying cause of hospital-acquired infections and represent a critical need for innovative antibacterial development. New oxopyrazole agents targeting penicillin-binding proteins (PBPs) based on a non-β-lactam core and incorporating a siderophore moiety (figure) which facilitates transport to the periplasm are being developed which show promise against Gram-negative organisms including Acinetobacter spp. Methods YU253911, an example of this new class of antibacterials, was characterized in vitro. Minimum inhibitory concentrations (MICs) were determined by broth microdilution against a collection of 200 previously described (whole-genome sequencing) Acinetobacter isolates including 98 carbapenem-resistant A. baumannii strains. YU253911’s antimicrobial activity was also evaluated in combination with complementary PBP agents and β-lactamase inhibitors by MIC and disc diffusion testing. All studies were performed according to current Clinical and Laboratory Standards Institute (CLSI) guidelines using iron-depleted media. Breakpoints for ceftazidime were arbitrarily chosen as reference. Results Using ceftazidime (breakpoint ≤8 μg/mL) as a comparator, 175 of the 200 Acinetobacter isolates were susceptible to YU253911, which possessed an MIC50 of 0.5 μg/mL and an MIC90 of 16 μg/mL. This compared favorably to all previously tested β-lactams including penicillins, cephalosporins, monobactams and carbapenems (MIC50s 2 to >16 μg/mL). Against the subset of carbapenem-resistant A. baumannii isolates, YU253911’s potency was similar with an MIC50 of 1 μg/mL. Genetic analysis showed β-lactamase genes, including OXA-23 and other carbapenemases, were common in both YU253911-resistant and susceptible strains. Conclusion YU253911 demonstrates promising in vitro potency against a collection of Acinetobacter isolates and compares favorably to β-lactam antibiotics. Understanding interactions with PBP agents and β lactamase inhibitors is being explored as well as further studies on the mechanism of resistance. Disclosures All authors: No reported disclosures.

scholarly journals Biological Evaluation of Newly Synthesized Biaryl Guanidine Derivatives to Arrest β-Secretase Enzymatic Activity Involved in Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Sayyad Ali ◽  
Muhammad Hassham Hassan Bin Asad ◽  
Fahad Khan ◽  
Ghulam Murtaza ◽  
Albert A. Rizvanov ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Evaluation ◽  
Morris Water Maze Test ◽  
Pharmacokinetic Parameters ◽  
The Novel ◽  
Object Recognition Test ◽  
Promising Target

Proteases BACE1 (β-secretases) enzymes have been recognized as a promising target associated with Alzheimer’s disease (AD). This study was carried out on the principles of molecular docking, chemical synthesis, and enzymatic inhibition of BACE1 enzymes via biaryl guanidine-based ligands. Based on virtual screening, thirteen different compounds were synthesized and subsequently evaluated via in vitro and in vivo studies. Among them, 1,3-bis(5,6-difluoropyridin-3-yl)guanidine (compound (9)) was found the most potent (IC50=97±0.91 nM) and active to arrest (99%) β-secretase enzymes (FRET assay). Furthermore, it was found to improve the novel object recognition test and Morris water maze test significantly (p<0.05). Improved pharmacokinetic parameters, viz., Log Po/w (1.76), Log S (-2.73), and better penetration to the brain (BBB permeation) with zero Lipinski violation, made it possible to hit the BACE1 as a potential therapeutic source for AD.

scholarly journals In VitroAntibacterial Activity of the Ceftazidime-Avibactam Combination against Enterobacteriaceae, Including Strains with Well-Characterized β-Lactamases

2015 ◽  
Vol 59 (4) ◽  
pp. 1931-1934 ◽  
Author(s):  
Premavathy Levasseur ◽  
Anne-Marie Girard ◽  
Christine Miossec ◽  
John Pace ◽  
Ken Coleman
Keyword(s):  
Antibacterial Activity ◽  
Antimicrobial Agents ◽  
The Novel ◽  
Content Type ◽  
Class A ◽  
Fixed Weight ◽  
Class D ◽  
Resistant Strains ◽  
Esbl Producers

ABSTRACTThe novel β-lactamase inhibitor avibactam is a potent inhibitor of class A, class C, and some class D enzymes. Thein vitroantibacterial activity of the ceftazidime-avibactam combination was determined for a collection ofEnterobacteriaceaeclinical isolates; this collection was enriched for resistant strains, including strains with characterized serine β-lactamases. The inhibitor was added either at fixed weight ratios to ceftazidime or at fixed concentrations, with the latter type of combination consistently resulting in greater potentiation of antibacterial activity. In the presence of 4 μg/ml of avibactam, the ceftazidime MIC50and MIC90(0.25 and 2 μg/ml, respectively) were both below the CLSI breakpoint for ceftazidime. Further comparisons with reference antimicrobial agents were performed using this fixed inhibitor concentration. Against most ceftazidime-susceptible and -nonsusceptible isolates, the addition of avibactam resulted in a significant increase in ceftazidime activity, with MICs generally reduced 256-fold for extended-spectrum β-lactamase (ESBL) producers, 8- to 32-fold for CTX-M producers, and >128-fold for KPC producers. Overall, MICs of a ceftazidime-avibactam combination were significantly lower than those of the comparators piperacillin-tazobactam, cefotaxime, ceftriaxone, and cefepime and similar or superior to those of imipenem.

scholarly journals Production of multiple bacteriocins, including the novel bacteriocin gassericin M, by Lactobacillus gasseri LM19, a strain isolated from human milk

2019 ◽  
Author(s):  
Enriqueta Garcia-Gutierrez ◽  
Paula M. O’Connor ◽  
Ian J. Colquhoun ◽  
Natalia M. Vior ◽  
Juan Miguel Rodríguez ◽  
...  
Keyword(s):  
Human Milk ◽  
Human Colon ◽  
Short Chain Fatty Acids ◽  
Antagonistic Activity ◽  
The Novel ◽  
Lactobacillus Gasseri ◽  
Potential Synergy ◽  
Interesting Candidate ◽  
Health Promoting

AbstractBacteriocins are antimicrobial peptides produced by bacteria and their production by health-promoting microbes is regarded as a desirable probiotic trait. We found that Lactobacillus gasseri LM19, a strain isolated from human milk, exhibits antagonistic activity against different enteropathogens and produces several bacteriocins, including a novel bacteriocin, gassericin M. These bacteriocins were purified from culture and synthesised to investigate their activity and potential synergy. L. gasseri LM19 was tested in a complex environment mimicking human colon conditions where it not only survived but expressed the seven bacteriocin genes and produced short chain fatty acids. Metagenomic analysis of these in vitro colon cultures showed that co-inoculation of L. gasseri LM19 with Clostridium perfringens gave profiles with more similarity to controls than to vessels inoculated with C. perfringens alone. This makes L. gasseri LM19 an interesting candidate for further study for maintaining homeostasis in the gut environment.

scholarly journals Inhibitory Effects of Lipopeptides and Glycolipids on C. albicans–Staphylococcus spp. Dual-Species Biofilms

2021 ◽  
Vol 11 ◽  
Author(s):  
Chiara Ceresa ◽  
Maurizio Rinaldi ◽  
Francesco Tessarolo ◽  
Devid Maniglio ◽  
Emanuele Fedeli ◽  
...  
Keyword(s):  
Metabolic Activity ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Soluble Form ◽  
Total Biomass ◽  
Chronic Infections ◽  
Host Immune Responses ◽  
Microbial Biofilms ◽  
Staphylococcus Spp

Microbial biofilms strongly resist host immune responses and antimicrobial treatments and are frequently responsible for chronic infections in peri-implant tissues. Biosurfactants (BSs) have recently gained prominence as a new generation of anti-adhesive and antimicrobial agents with great biocompatibility and were recently suggested for coating implantable materials in order to improve their anti-biofilm properties. In this study, the anti-biofilm activity of lipopeptide AC7BS, rhamnolipid R89BS, and sophorolipid SL18 was evaluated against clinically relevant fungal/bacterial dual-species biofilms (Candida albicans, Staphylococcus aureus, Staphylococcus epidermidis) through quantitative and qualitative in vitro tests. C. albicans–S. aureus and C. albicans–S. epidermidis cultures were able to produce a dense biofilm on the surface of the polystyrene plates and on medical-grade silicone discs. All tested BSs demonstrated an effective inhibitory activity against dual-species biofilms formation in terms of total biomass, cell metabolic activity, microstructural architecture, and cell viability, up to 72 h on both these surfaces. In co-incubation conditions, in which BSs were tested in soluble form, rhamnolipid R89BS (0.05 mg/ml) was the most effective among the tested BSs against the formation of both dual-species biofilms, reducing on average 94 and 95% of biofilm biomass and metabolic activity at 72 h of incubation, respectively. Similarly, rhamnolipid R89BS silicone surface coating proved to be the most effective in inhibiting the formation of both dual-species biofilms, with average reductions of 93 and 90%, respectively. Scanning electron microscopy observations showed areas of treated surfaces that were free of microbial cells or in which thinner and less structured biofilms were present, compared to controls. The obtained results endorse the idea that coating of implant surfaces with BSs may be a promising strategy for the prevention of C. albicans–Staphylococcus spp. colonization on medical devices, and can potentially contribute to the reduction of the high economic efforts undertaken by healthcare systems for the treatment of these complex fungal–bacterial infections.

scholarly journals In vitro activity of the siderophore cephalosporin, cefiderocol, against molecularly characterized, carbapenem-non-susceptible Gram-negative bacteria from Europe

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Christopher Longshaw ◽  
Davide Manissero ◽  
Masakatsu Tsuji ◽  
Roger Echols ◽  
Yoshinori Yamano
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Similar Proportion ◽  
Gram Negative Bacteria ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Gene Profiles ◽  
Carbapenemase Gene

Abstract Objectives Many carbapenem-resistant (CR) Gram-negative (GN) pathogens exhibit MDR, meaning few therapeutic options are available for CR-GN infections. Cefiderocol, a siderophore cephalosporin, has demonstrated in vitro efficacy against CR-GN bacteria. In the SIDERO-CR-2014–2016 surveillance study, European clinical isolates comprising carbapenem-non-susceptible (CarbNS) Enterobacterales and MDR non-fermenters were tested against cefiderocol and comparators. Methods Cefiderocol MICs were determined using iron-depleted CAMHB, and comparators using CAMHB, per recommended CLSI methodology. Carbapenemase gene profiles were determined using PCR. Results Isolates (N = 870) from 23 European countries comprised CarbNS Enterobacterales (n = 457), MDR Pseudomonas aeruginosa (n = 177) and MDR Acinetobacter baumannii (n = 236). The most common carbapenemases were KPC (52%), OXA-48-like (19%), VIM (14%) and NDM (8%) in Enterobacterales, VIM (41%) in P. aeruginosa and OXA-23-like (57%) and OXA-24/40-like (37%) in A. baumannii. Most carbapenemase-producing isolates (65%) co-carried ESBLs. Approximately half of P. aeruginosa isolates were negative for carbapenemases, compared with 10% of Enterobacterales and 3% of A. baumannii. A similar proportion of Enterobacterales were susceptible to cefiderocol (81.6%; 79.0% of VIM producers; 51.4% of NDM producers; based on EUCAST breakpoint values) compared with comparator antimicrobial agents, including colistin (76.4%; 93.5% of VIM producers; 78.4% of NDM producers) and ceftazidime/avibactam (76.6%; 1.6% of VIM producers; 2.7% of NDM producers). Of P. aeruginosa isolates, 98.3% were susceptible to cefiderocol (100% of VIM producers), similar to colistin (100%). Against A. baumannii, 94.9% had cefiderocol MIC ≤2 mg/L and 93.6% of isolates were susceptible to colistin. Conclusions Cefiderocol demonstrated potent activity against CarbNS and MDR GN bacteria, including non-fermenters and a wide variety of MBL- and serine-β-lactamase-producing strains.

Ceftazidime/avibactam and eravacycline susceptibility of carbapenem-resistant Klebsiella pneumoniae in two Greek tertiary teaching hospitals

2021 ◽  
Author(s):  
Maria Chatzidimitriou ◽  
Panagiota Chatzivasileiou ◽  
Georgios Sakellariou ◽  
MariaAnna Kyriazidi ◽  
Asimoula Kavvada ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Antimicrobial Agents ◽  
Carbapenem Resistance ◽  
Teaching Hospitals ◽  
Diffusion Method ◽  
Strain Identification ◽  
Disk Diffusion Method ◽  
Carbapenem Resistant ◽  
Tertiary Teaching

AbstractThe present study evaluated the carbapenem resistance mechanisms of Klebsiella pneumoniae strains isolated in two Greek tertiary teaching hospitals and their susceptibility to currently used and novel antimicrobial agents.Forty-seven carbapenem resistant K. pneumoniae strains were collected in G. Papanikolaou and Ippokrateio hospital of Thessaloniki between 2016 and 2018. Strain identification and antimicrobial susceptibility was conducted by Vitek 2 system (Biomérieux France). Susceptibility against new antimicrobial agents was examined by disk diffusion method. Polymerase chain reaction (PCR) was used to detect blaKPC, blaVIM, blaNDM and blaOXA-48 genes.The meropenem–EDTA and meropenem–boronic acid synergy test performed on the 24 K. pneumoniae strains demonstrated that 8 (33.3%) yielded positive for metallo-beta-lactamases (MBL) and 16 (66.6%) for K. pneumonia carbapenemases (KPC) production. Colistin demonstrated the highest in vitro activity (87.7%) among the 47 K. pneumoniae strains followed by gentamicin (76.5%) and tigecycline (51%). Among new antibiotics ceftazidime/avibactam showed the highest sensitivity (76.6%) in all strains followed by eravacycline (66.6%). The blaKPC gene was present in 30 strains (63.8%), the blaNDM in 11 (23.4%) and the blaVIM in 6 (12.8%). The blaOXA-48 gene was not detected.Well established antimicrobial agents such as colistin, gentamicin and tigecycline and novel antibiotics like ceftazidime/avibactam and eravacycline can be reliable options for the treatment of invasive infections caused by carbapenem-resistant K. pneumoniae.

scholarly journals Synergy of Silver Nanoparticles and Aztreonam against Pseudomonas aeruginosa PAO1 Biofilms

2014 ◽  
Vol 58 (10) ◽  
pp. 5818-5830 ◽  
Author(s):  
Marc B. Habash ◽  
Amber J. Park ◽  
Emily C. Vis ◽  
Robert J. Harris ◽  
Cezar M. Khursigara
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Silver Nanoparticles ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Cell Envelope ◽  
Antimicrobial Properties ◽  
Planktonic Cell ◽  
Chronic Infections ◽  
Content Type

ABSTRACTPathogenic bacterial biofilms, such as those found in the lungs of patients with cystic fibrosis (CF), exhibit increased antimicrobial resistance, due in part to the inherent architecture of the biofilm community. The protection provided by the biofilm limits antimicrobial dispersion and penetration and reduces the efficacy of antibiotics that normally inhibit planktonic cell growth. Thus, alternative antimicrobial strategies are required to combat persistent infections. The antimicrobial properties of silver have been known for decades, but silver and silver-containing compounds have recently seen renewed interest as antimicrobial agents for treating bacterial infections. The goal of this study was to assess the efficacy of citrate-capped silver nanoparticles (AgNPs) of various sizes, alone and in combination with the monobactam antibiotic aztreonam, to inhibitPseudomonas aeruginosaPAO1 biofilms. Among the different sizes of AgNPs examined, 10-nm nanoparticles were most effective in inhibiting the recovery ofP. aeruginosabiofilm cultures and showed synergy of inhibition when combined with sub-MIC levels of aztreonam. Visualization of biofilms treated with combinations of 10-nm AgNPs and aztreonam indicated that the synergistic bactericidal effects are likely caused by better penetration of the small AgNPs into the biofilm matrix, which enhances the deleterious effects of aztreonam against the cell envelope ofP. aeruginosawithin the biofilms. These data suggest that small AgNPs synergistically enhance the antimicrobial effects of aztreonam againstP. aeruginosain vitro, and they reveal a potential role for combinations of small AgNPs and antibiotics in treating patients with chronic infections.

scholarly journals Studies of the Novel Ketolide ABT-773: Transport, Binding to Ribosomes, and Inhibition of Protein Synthesis inStreptococcus pneumoniae

2000 ◽  
Vol 44 (6) ◽  
pp. 1562-1567 ◽  
Author(s):  
John O. Capobianco ◽  
ZhenSheng Cao ◽  
Virginia D. Shortridge ◽  
ZhenKun Ma ◽  
Robert K. Flamm ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
The Novel ◽  
In Vitro Activity ◽  
Wild Type ◽  
Ribosome Binding ◽  
New Class ◽  
Resistant Phenotype

ABSTRACT Macrolide resistance in Streptococcus pneumoniae has been associated with two main mechanisms: target modification by Erm methyltransferases and efflux by macrolide pumps. The ketolide ABT-773, which has a 3-keto group and no l-cladinose sugar, represents a new class of drugs with in vitro activity against a variety of resistant bacteria. Several approaches were undertaken to understand how ABT-773 was able to defeat resistance mechanisms. We demonstrated tighter ribosome binding of ABT-773 than erythromycin. We also showed that ABT-773 (i) accumulated in macrolide-sensitiveS. pneumoniae at a higher rate than erythromycin, (ii) was able to bind with methylated ribosomes, though at lower affinities than with wild-type ribosomes, and (iii) accumulated in S. pneumoniae strains with the efflux-resistant phenotype.

scholarly journals In Vitro Antibacterial Activity of Galla Chinensis Combined with Different Antibacterial Drugs against Carbapenem-Resistant E.Coli

2019 ◽  
Vol 2 (4) ◽  
pp. 15
Author(s):  
Zhizhi Xie ◽  
Changzhi Xu ◽  
Yanhua Yi ◽  
Donglin Zhu ◽  
Yun Xi
Keyword(s):  
Antibacterial Activity ◽  
Synergistic Effect ◽  
Antimicrobial Agents ◽  
Additive Effect ◽  
Dilution Method ◽  
Antagonistic Effects ◽  
Carbapenem Resistant ◽  
Combined Use ◽  
In Vitro Antibacterial Activity

Objective: To evaluate the antibacterial effects of meropenem and levofloxacin respectively combined with Galla chinensis on carbapenem-resistant Escherichia coli in vitro. Methods： The protocol was designed with checkerboard method and the carbapenem-resistant E.coli was isolated in our hospital. The minimum inhibitory concentrations(MICs) of G. chinensis alone and combined with 2 antimicrobial agents against carbapenem-resistant E.coli were determined by broth dilution method and the fractional inhibitory concentration index (FICI) was calculated according to MICs results. Result： the combined use of G. chinensis and meropenem (or levofloxacin) significantly decreased both MIC50 and MIC90; After the combination of G. chinensis and meropenem, the synergistic effect was 86.7%, and the additive effect was 13.3%, no irrelevant and antagonistic effects. After combined use of G. chinensis and levofloxacin, the synergistic effect was 66.7%, and the additive effect was 33.3%. No irrelevant and antagonistic effects. Conclusion： Galla chinensis combined with meropenem or levofloxacin has synergistic and additive antibacterial effect, with certain combined antibacterial activity.

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