Search results for "Lactams"
showing 10 items of 54 documents
Gut microbiota disturbance during antibiotic therapy: a multi-omic approach
2014
It is known that the gastrointestinal tract (GIT) microbiota responds to different antibiotics in different ways and that while some antibiotics do not induce disturbances of the community, others drastically influence the richness, diversity, and prevalence of bacterial taxa. However, the metabolic consequences thereof, independent of the degree of the community shifts, are not clearly understood. In a recent article, we used an integrative OMICS approach to provide new insights into the metabolic shifts caused by antibiotic disturbance. The study presented here further suggests that specific bacterial lineage blooms occurring at defined stages of antibiotic intervention are mostly associa…
Synergistic effect between amoxicillin and TLR ligands on dendritic cells from amoxicillin-delayed allergic patients.
2013
Journal Article; Amoxicillin, a low-molecular-weight compound, is able to interact with dendritic cells inducing semi-maturation in vitro. Specific antigens and TLR ligands can synergistically interact with dendritic cells (DC), leading to complete maturation and more efficient T-cell stimulation. The aim of the study was to evaluate the synergistic effect of amoxicillin and the TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively) in TLR expression, DC maturation and specific T-cell response in patients with delayed-type hypersensitivity (DTH) reactions to amoxicillin. Monocyte-derived DC from 15 patients with DTH to amoxicillin and 15 controls were cultured with amoxicillin in the pr…
DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current -Lactam Antibiotic Doses Sufficient for Critically Ill Patients?
2014
Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether α-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome.Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 α-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% f TMIC) an…
Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (C…
2019
Background and aims Limited data are available on the effectiveness and tolerability of direct-acting antivirals (DAAs) therapies in the real world for HCV-infected patients with comorbidities. This study aimed to describe the effectiveness of OBV/PTV/r +/- DSV (3D/2D regimen) with or without ribavirin (RBV) in HCV or HCV/HIV co-infected patients with GT1/GT4 and CKD (IIIb-V stages), including those under hemodialysis and peritoneal dialysis in routine clinical practice in Spain in 2015. Material and methods Non-interventional, retrospective, multicenter data collection study in 31 Spanish sites. Socio-demographic, clinical variables, study treatment characteristics, effectiveness and toler…
Therapeutic Strategies To Counteract Antibiotic Resistance in MRSA Biofilm‐Associated Infections
2021
Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the leading causes of persistent human infections. This pathogen is widespread and is able to colonize asymptomatically about a third of the population, causing moderate to severe infections. It is currently considered the most common cause of nosocomial infections and one of the main causes of death in hospitalized patients. Due to its high morbidity and mortality rate and its ability to resist most antibiotics on the market, it has been termed a “superbug”. Its ability to form biofilms on biotic and abiotic surfaces seems to be the primarily means of MRSA antibiotic resistance and pervasiveness. Importantly, more tha…
Sequence type 101 (ST101) as the predominant carbapenem-non-susceptible Klebsiella pneumoniae clone in an acute general hospital in Italy.
2012
Klebsiella pneumoniae is one of the most common multidrug-resistant (MDR) Gram-negative organisms worldwide, responsible for high morbidity and mortality both in hospitals and alternative healthcare settings. Recently, increasing use of carbapenems has promoted the emergence and dissemination of carbapenem-non-susceptible MDR K. pneumoniae strains. All of the CNSKP strains isolated between January 2009 and December 2011 in the General Hospital of Prato (Prato, Italy) were studied. Our findings indicate that, unlike previously reported by other authors from different regions of Italy, K. pneumoniae producing KPC-2 and belonging to ST101 have been established in the area of Prato, Tuscany, It…
New β-Lactam-β-Lactamase Inhibitor Combinations.
2020
The limited armamentarium against drug-resistant Gram-negative bacilli has led to the development of several novel β-lactam-β-lactamase inhibitor combinations (BLBLIs). In this review, we summarize their spectrum of in vitro activities, mechanisms of resistance, and pharmacokinetic-pharmacodynamic (PK-PD) characteristics. A summary of available clinical data is provided per drug. Four approved BLBLIs are discussed in detail. All are options for treating multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa Ceftazidime-avibactam is a potential drug for treating Enterobacterales producing extended-spectrum β-lactamase (ESBL), Klebsiella pneumoniae carbapenemase (KPC), AmpC, an…
Synthesis of enantiopure pyrrolidine-derived peptidomimetics and oligo-beta-peptides via nucleophilic ring-opening of beta-lactams.
2006
The synthesis of the two enantiomers of pyrrolidine-derived spiro beta-lactams by resolution with D- and L-Boc phenylalanine is described. The potential of these optically active spiro beta-lactams on the synthesis of peptidomimetics as analogues of melanostatin is evaluated. Theoretical studies of several models, at the Becke3LYP/6-31+G* level of theory, together with previous experimental evidences from our group, gathered by NMR, allow us to design structures that can efficiently mimic some biologically active peptide-type molecules. On the other hand, the spiro beta-lactams have shown their utility in the preparation of beta-peptides. As an example, a homo-tetra-beta-peptide was synthes…
Role of Protein Flexibility in Enzymatic Catalysis: Quantum Mechanical−Molecular Mechanical Study of the Deacylation Reaction in Class A β-Lactamases
2002
We present a theoretical study of a mechanism for the hydrolysis of the acyl-enzyme complex formed by a class A beta-lactamase (TEM1) and an antibiotic (penicillanate), as a part of the process of antibiotic's inactivation by this type of enzymes. In the presented mechanism the carboxylate group of a particular residue (Glu166) activates a water molecule, accepting one of its protons, and afterward transfers this proton directly to the acylated serine residue (Ser70). In our study we employed a quantum mechanics (AM1)-molecular mechanics partition scheme (QM/MM) where all the atoms of the system were allowed to relax. For this purpose we used the GRACE procedure in which part of the system …
Inside the Hsp90 inhibitors binding mode through induced fit docking
2009
Abstract During the last few decades, the development of new anticancer strategies had to face the instability of many tumors, occurring when the genetic plasticity of cells produces new drug-resistant cancers. It has been shown that a chaperone protein, heat shock protein 90 (Hsp90), is one of the fundamental factors involved in the cell response to stresses, and its role in many biochemical pathways has been demonstrated. Thus, the inhibition of Hsp90 represents a new target of antitumor therapy, since it may influence many specific signaling pathways. The natural antibiotic Geldanamycin is the first Hsp90 inhibitor that has been identified. Nevertheless, more potent and water-soluble sma…