Antibiotics (Properties, Application, Interaction) - Posokhova K.A., Viktorov O.P. 2005

Other Antibiotics
Oxazolidinones

The oxazolidinone group is a novel Class of synthetic antimicrobials that exhibit potent activity against gram-positive microorganisms, including those resistant to all Other Antibiotics. Linezolid serves as a prime representative of the oxazolidinones.

The MECHANISM OF ACTION involves the inhibition of microbial Protein Synthesis at the Cytology/cytology/16.html">Early stages of Translation (it binds irreversibly to the 30S and 50S ribosomal subunits).

THE SPECTRUM OF activity encompasses most aerobic and anaerobic gram-positive microorganisms. Linezolid is highly active against methicillin-resistant S. aureus (MRS), coagulase-negative staphylococci (CNS)—including oxacillin-resistant and glycopeptide-intermediate strains (GISA)—and effectively targets enterococci, including vancomycin- and teicoplanin-resistant strains (VRE). It is active against both susceptible and antibiotic-resistant strains of Streptococcus spp., Nocardia spp., L. monocytogenes, Peptostreptococcus spp., Clostridium spp. (including C. perfringens and C. difficile). Linezolid exerts a bactericidal effect on S. pneumoniae, including strains resistant to penicillin, erythromycin, ceftriaxone, tetracycline, chloramphenicol, and clindamycin. To date, no linezolid-resistant microorganisms have been identified. Owing to its unique antibacterial mechanism of action, there is no cross-resistance between linezolid and other antibiotic classes, such as Tetracyclines, chloramphenicol, macrolides, Lincosamides, Aminoglycosides, and Streptogramins.

Pharmacokinetics. The drug has a 100% oral bioavailability, which is unaffected by food intake. It is widely distributed throughout the body, with peak Blood concentrations achieved within 1-2 hours. The half-life (T_1/2) is 4-5 hours and remains virtually unchanged in renal impairment.

Linezolid is indicated for the Treatment of Infections caused by multidrug-resistant gram-positive flora, primarily staphylococcal (including those caused by MRS and CNS) and enterococcal infections. For pathologies caused by VRE, linezolid, alongside quinupristin/dalfopristin (Synercid), is a drug of choice.

Indications for linezolid use:

- infections caused by vancomycin-resistant strains of E. faecalis—abdominal infections, Sepsis, including catheter-associated sepsis;

- nosocomial Pneumonia caused by S. aureus strains (methicillin-susceptible or methicillin-resistant) or penicillin-resistant S. pneumoniae; linezolid (at a dose of 600 mg twice daily) is comparable in efficacy to vancomycin (1.0 g twice daily) while offering better tolerability;

- complicated Skin and soft tissue infections caused by S. aureus (methicillin-susceptible or resistant strains), S. pyogenes, S. agalactiae;

- community-acquired pneumonia caused by S. pneumoniae, including cases complicated by sepsis, as well as pneumonia caused by methicillin-susceptible S. aureus strains.

- Urinary Tract infections;

- endocarditis.

Generalized indications for use and treatment regimens for linezolid are presented in Table 44.

Table 44. Linezolid Dosing Regimens (S.V. Budanov, L.B. Smirnova, 2002).

When treating conditions caused by mixed flora in the presence of gram-negative pathogens, linezolid should be used in combination with third- or fourth-generation Cephalosporins or fluoroquinolones.

Another oxazolidinone derivative, eperezolid, is currently undergoing clinical investigation.

Despite the high antibacterial activity of linezolid in the most severe forms of infectious diseases, this agent should not be used without sufficient justification. It should be reserved for the treatment of infections caused by laboratory-confirmed multidrug-resistant strains, or for the management of severe complications caused by pathogens resistant to first-line agents.