Linezolid: a promising option in the treatment of Gram-positives (original) (raw)
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Linezolid: its role in the treatment of gram-positive, drug-resistant bacterial infections
American family physician, 2002
While the choices available for the management of gram-positive, drug-resistant bacterial infections are becoming limited, antimicrobial resistance is becoming increasingly problematic because of the widespread overuse of antibiotics. Linezolid is a synthetic antibiotic belonging to a new class of antimicrobials called the oxazolidinones. Linezolid disrupts bacterial growth by inhibiting the initiation process of protein synthesis--a mechanism of action that is unique to this class of drugs. It is well absorbed with high bioavailability that allows conversion to oral therapy as soon as the patient is clinically stable. It has been approved for certain gram-positive infections including certain drug-resistant enterococcus, staphylococcus, and pneumococcus strains. It is generally well tolerated, with myelosuppression being the most serious adverse effect. As a nonselective inhibitor of monoamine oxidase, caution is recommended when used with adrenergic or serotonergic agents (e.g., t...
Linezolid use in Medicin Therapy against Multiresistant Bacteria-A Review
Journal of Bacteriology & Parasitology, 2017
After the description of an element with ability to combat the infectious processes originating from bacteria, starts a race for survival between the interrelationship of species, bacterial and human. With the evolution scientifictechnical, the man was able to synthesize new antibacterial substances, on the other hand the mechanisms of gene evolution enabled the emergence of multidrug-resistant bacteria. Some of this organisms are frequent on hospital environment and have high adaptability to new drugs, such as Staphylococcus aureus and Enterococcus spp. resistant to oxacillin and vancomycin, considered drugs of choice against multidrug-resistant microorganisms. So, a new antibiotics class was developed, superior to vancomycin and oxazolidinone, the linezolid. Thus, the present study aimed at understanding the use of linezolid in drug therapy against multi-resistant bacteria. To perform this study, a literature review of last 10 years was performed. In 2002, after the liberation of the use of linezolid as treatment for infectious processes against gram-positive bacteria, this drug was commonly used throughout the world. Similarly, the pressure of natural selection stood out, and there were records of resistant strains to linezolid. As prospects for control of infections caused by these resistant strains, was approved by the FDA in 2014 the use of drugs with linezolid resistant anti-strains activity. However, we conclude that, in addition to natural selection and genetic variation process, human behavior regarding the use of antibiotics, increases the selection of resistant microorganisms to antibiotic, including linezolid.
Linezolid and its derivatives: the promising therapeutic challenge to multidrug-resistant pathogens
2018
Linezolid is the main drug representative of the oxazolidinones, widely used in the clinical practice to treat severe Gram-positive infections for some decades. The uniquely particular mechanism of action of Linezolid, with a block of ribosomal assembling before the initiation of bacterial protein synthesis has been studied in various bacteria and linked mainly to mutations in the ribosomal 50S subunit. Over the years, a large amount of clinical and pharmacokinetic data have been accumulated, relating to linezolid use in different patient groups (obesity, enteral feeding, renal failure, neonates, and paediatrics) and in different clinical conditions (sepsis syndrome, skin and soft tissue infection, diabetic foot infection, pneumonia, bone and joint infection, infection of the central nervous system, eye infection, and neutropenic sepsis). In 2001 Linezolid resistance started emerging in Staphylococcus aureus and Enterococcus faecium clinical isolates and once again the attention of ...
International Journal of Antimicrobial Agents, 2001
Background: Staphylococcus is responsible for a variety of medical problems, including skin and softtissue infections (SSTIs), surgical site infections (SSIs), endocarditis and hospital acquired bacteraemia. Methicillin resistance in staphylococcus has become a global problem limiting the treatment modalities to a large extent. Methods: The aim of this study was to evaluate the in vitro activity of linezolid and other antibiotics against clinical isolates of methicillin resistant staphylococcus (n=163); including 105 methicillin resistant Staphylococcus aureus and 58 methicillin resistant coagulase negative staphylococci. Antibiogram of these isolates was determined by the Kirby-Bauer disc diffusion method and minimum inhibitory concentration of linezolid was determined by standard agar dilution method. Results: Overall methicillin resistant S. aureus showed high multi-drug resistance. ATCC 25923 Staphylococcus aureus and ATCC 29213 Staphylococcus aureus were used as the standard control strains. MIC 90 of linezolid was comparable for methicillin resistant coagulase negative staphylococci and methicillin resistant S. Aureus (4.0 mg/L); however at MIC 50 linezolid was two fold more active against methicillin resistant coagulase negative staphylococci (1mg/L) than methicillin resistant S. aureus (2mg/L). Conclusion: It is concluded that linezolid has excellent activity against methicillin resistant staphylococci including multidrug resistant strains.
Linezolid for the treatment of infections caused by Gram-positive pathogens in China
International Journal of Antimicrobial Agents, 2008
In this randomised, double-blind, comparator-controlled, multicentre study conducted in China, 142 hospitalised patients aged 18-75 years with pneumonia (n = 80) or complicated skin and soft-tissue infection (cSSTI) (n = 62) due to suspected or known Gram-positive pathogens were randomised (1:1) to receive either linezolid 600 mg (n = 71) or vancomycin 1 g in patients aged ≤60 years or 0.75 g in patients aged >60 years (n = 71) intravenously every 12 h. The duration of treatment was 10-21 days for patients with pneumonia and 7-21 days for patients with cSSTI. Clinical outcomes were assessed at end-of-treatment (EOT) visit and follow-up (FU) visit 7-28 days post therapy. Staphylococcus aureus was the most common pathogen at baseline and most of these isolates were resistant to meticillin. All isolates were susceptible to linezolid and vancomycin. For the evaluable patients, the effective treatment rate for linezolid was higher than that for vancomycin at EOT (86.9% (53/61) vs. 61.7% (37/60)) and at FU (83.1% (49/59) vs. 64.9% (37/57)). Pathogen eradication rates for the microbiologically evaluable patients at FU were 79.2% (42/53) for linezolid and 61.5% (32/52) for vancomycin. The incidence of drug-related adverse events (AEs) was 25.4% (18/71) for linezolid and 16.9% (12/71) for vancomycin. Four (5.6%) linezolid-treated and eight (11.3%) vancomycin-treated patients discontinued the study drug because of an AE. Linezolid was well tolerated and effective for the treatment of infections caused by Gram-positive pathogens, including meticillin-resistant S. aureus.
Association of Pharmacokinetic and Pharmacodynamic Aspects of Linezolid with Infection Outcome
Current Drug Metabolism, 2009
Linezolid is the first antibiotic of a new class (oxazolidinones). It inhibits protein synthesis by binding to the bacterial 23S ribosomal RNA of the 50S subunit, thus blocking the formation of the functional 70S initiation complex, but it does not inhibit peptidyl transferase. Therefore, its mechanism of action is unique and cross resistance is unlikely to occur; however, resistant strains have already been reported, but the rate of resistance is low in surveillance programs. Linezolid has a favorable pharmacokinetic profile. It is rapidly absorbed when administered orally, and it is 100% bioavailable, thus allowing early switch from intravenous to oral administration. The maximum plasma concentration (range between 13.1±1.8 to 19.5±4.5 μg/ml according to the route of administration, studied population and dosages administered to subjects) is achieved 1-2 hours after the first dosage. It penetrates readily to most tissues of the human body at concentrations much higher than that of the minimal inhibitory concentrations of the targeted pathogens. It is metabolized by oxidation in two major inactive metabolites and is eliminated mainly through the kidneys. Linezolid is bacteriostatic for staphylococci and enterococci but bactericidal for pneumococci and kills bacteria in a time-dependent fashion. It has been studied in several randomized controlled trials and has been approved for the treatment of patients with Gram positive bacterial infections (community-acquired and nosocomial pneumonia, skin and soft tissue infections, and infections due to vancomycin-resistant enterococci) including these due to multidrug-resistant strains. Careful and judicious use is warranted to preserve the activity of this important antibiotic.
Linezolid Resistance in Staphylococci
Pharmaceuticals, 2010
Linezolid, the first oxazolidinone to be used clinically, is effective in the treatment of infections caused by various Gram-positive pathogens, including multidrug resistant enterococci and methicillin-resistant Staphylococus aureus. It has been used successfully for the treatment of patients with endocarditis and bacteraemia, osteomyelitis, joint infections and tuberculosis and it is often used for treatment of complicated infections when other therapies have failed.
1999
The emergence of resistance in gram-positive bacteria has necessitated a search for new antimicrobial agents. Linezolid is an oxazolidinone, a new class of antibacterial agents with enhanced activity against pathogens. We compared the activity of linezolid to those of other antimicrobial agents against 3,945 clinical isolates. Linezolid demonstrated potent activity against all isolates tested. For all vancomycin-susceptible enterococci, staphylococci, and streptococci, the activity of linezolid was comparable to that of vancomycin. Against oxacillin-resistant staphylococci and vancomycin-resistant enterococci, linezolid was the most active agent tested. In summary, linezolid appears to be a promising new antimicrobial agent for the treatment of gram-positive infections.