Recent development of potent analogues of oxazolidinone antibacterial agents.

Dec 2012

 

Michalska K, Karpiuk I, Król M, Tyski S.

Source

Department of Antibiotics and Microbiology, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland. Electronic address: kmichalska@il.waw.pl.

Abstract

The oxazolidinones are a new and potent class of antimicrobial agents with activity mainly against Gram-positive strains. The commercial success of linezolid, the only FDA-approved oxazolidinone, has prompted many pharmaceutical companies to devote resources to this area of investigation. Until now, four types of chemical modifications of linezolid and oxazolidinone-type antibacterial agents, including modification on each of the A-(oxazolidinone), B-(phenyl), and C-(morpholine) rings as well as the C-5 side chain of the A-ring substructure, have been described. Division into sections according to side chain modification or the type of ring will be used throughout this review, although the process of synthesis usually involves the simultaneous modification of several elements of the linezolid substructure; therefore, assignment into the appropriate section depends on the structure-activity relationships (SAR) studies. This review makes an attempt to summarise the work carried out in the period from 2006 until mid-2012.

PubMed

Comparative urinary bactericidal activity of oral antibiotics against gram-positive pathogens.

May-June 2012

[Article in Croatian]

Bedenić B, Budimir A, Gverić A, Plecko V, Vranes J, Bubonja-Sonje M, Kalenić S.

Source

Zavod za mikrobiologiju, Medicinski fakultet Sveucilista u Zagrebu. branka.bedenic@zg.t-com.hr

Abstract

In routine bacteriological laboratories the antibacterial activity of antibiotics is determined by in vitro testing, usually by disk-diffusion test. However, in vitro testing does not always reflect antibacterial efficiency of antibiotics in vivo. In this investigation, the urine samples obtained in a single oral dose pharmacokinetic study were examined for their bactericidal activity against a range of relevant Gram-positive urinary tract pathogens. Urinary bactericidal activity of linezolid had been previously compared with ciprofloxacin but not with other oral antibiotics such as beta-lactams. Linezolid showed satisfactory urinary bactericidal titres throughout the whole testing period against all Gram-positive cocci. Fluoroquinolones displayed high and persisting levels of urinary bactericidal activity against staphylococci, but their activity against enterococci was weaker. According to the results of ex-vivo testing amoxycillin could be recommended only for infections caused by E. faecalis. Amoxycillin combined with clavulanic acid can be considered as a therapeutic option for infections caused by S. saprophyticus and E. faecalis. Older cephalosporins had high titres only against S. saprophyticus. Their drawback is a short elimination half-time in urine resulting in rapid decrease of urinary bactericidal titers during dosing interval. Furthermore, they do not show activity against enterococci due to their intrinsic resistance to cephalosporins.

PubMed

Effects of tigecycline, linezolid and vancomycin on biofilms of viridans streptococci isolates from patients with endocarditis.

Effects of tigecycline, linezolid and vancomycin on biofilms of viridans streptococci isolates from patients with endocarditis.

Int J Artif Organs. 2007 Sep

Presterl E, Lassnigg A, Eder M, Reichmann S, Hirschl AM, Graninger W.
Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna - Austria and Institute of Hygiene and Medical Microbiology, Division of Clinical Microbiology, Medical University of Vienna, Vienna - Austria.

Background: Endocarditis, and prosthetic valve endocarditis in particular, is a serious disease with high morbidity and mortality. We investigate the effects of tigecycline, linezolid and vancomycin on biofilms of viridans group streptococci (VGS) isolated from patients with definite native or prosthetic valve endocarditis.

Methods and Results: Ten of 20 VGS blood stream isolates from patients with endocarditis formed biofilms in the microtiter plate biofilm model. The minimal inhibitory concentrations (MIC) for tigecycline, linezolid and vancomycin were determined using the microdilution broth method. Biofilms were grown for 24 hours and were incubated with tigecycline, linezolid and vancomycin at increasing concentrations from 1-128x MIC of the isolate being tested. Biofilm thickness was quantified by measuring the optical density (OD) after dyeing it with crystal violet. The incubation of the biofilms with tigecycline, linezolid or vancomycin resulted in a significant reduction of OD compared to the control biofilm without antibiotic (p<0.05).>

Conclusions: In the present study on viridans streptococci isolated from patients with endocarditis, tigecycline and linezolid reduced the density of the biofilms as effectively as vancomycin. However, linezolid and vancomycin were bactericidal at higher concentrations. Linezolid and vancomycin at very high doses may be useful in the treatment of biofilm-associated diseases caused by VGS infections.

PMID: 17918125 [PubMed - as supplied by publisher]

Linezolid: a new antibiotic for newborns and children?

Linezolid: a new antibiotic for newborns and children?
J Chemother. 2006 Dec

Cuzzolin L,
Fanos V.

Department of Medicine & Public Health, University of Verona, Italy.

Staphylococcus aureus remains one of the most common and troublesome microorganisms causing disease in humans, despite the development of effective antibiotics. Linezolid is a member of a new class of synthetic antibiotics called oxazolidinones, introduced into therapy due to the increasing resistance of Gram-positive pathogens to traditional antibiotics. Information about the pharmacokinetics and tolerability profile of linezolid in the pediatric population mostly derive from adult studies and especially in the neonatal field relatively few data are available. Here we summarize linezolid's characteristics and report data available in the literature regarding linezolid use in newborns and children. For this purpose, a Medline search was performed between 1990 and 2006 involving the term "linezolid" combined with the terms "newborn", "infant", "child", "pediatrics". Additional information was obtained from Reactions Weekly.

PMID: 17267334 [PubMed - in process]

Related Article:

Use of linezolid in children: an overview of recent advances.

Expert Rev Anti Infect Ther. 2006 Dec

Velissariou IM.
P and A Kyriakou Children's Hospital, Amphitritis, Street 3, 17561, Palio Faliro, Athens, Greece. jane_vel@hotmail.com

Linezolid is the first member of a new generation of antibiotics, the synthetic oxazolidinones, to become available, with a broad spectrum of in vitro activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and vancomycin-resistant E. faecium. Linezolid is showing great promise currently for the treatment of multiresistant gram-positive bacterial infections, especially complicated skin infections, catheter-induced bacteremia or nosocomial pneumonia both in the community and in a hospital setting, in children and in adults. Although most recent reports are favorable and anticipatory of a more extensive use of linezolid in appropriately selected pediatric population groups in the near future, following treatment failure of conventional antimicrobial agents, more clinical trials are, however, required to investigate the safety profile and tolerability of this new antibiotic in the pediatric population.

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