Drug resistance linezolid

Treatment for septic patients with hospital-acquired, ventilator-acquired, and health care-associated pneumonia is dependent on risk factors for multi-drug resistant (MDR) organisms (Fig. 79-2). Recommended treatment for patients with no MDR risk factors are third-generation cephalosporins, fluoroquinolones, ampicillin-sulbactam, or ertapenem (see Table 79-3).35 Recommended treatment for patients with MDR risk factors are P-lactam/p-lactamase inhibitors (piperacillin-tazobactam), antipseudomonal cephalosporin, or carbapenem, plus an aminoglycoside, plus vancomycin or linezolid (see Table 79-3).35 If an aminoglycoside is undesirable, a antipseudomonal fluoroquinolone may be utilized with a P-lactam/p-lactamase inhibitor. 

Tahir N. Serotonin syndrome as consequence drug resistant infections an interaction between linezolid and citalopram. J Am Med Directors Assoc 2004 5 111-3. 

Linezolid is available in oral and parenteral formulations for treatment of VRSA, VRE, and drug-resistant pneumococci. 

Linezolid should be reserved as an alternative agent for infections caused by multiple-drug-resistant strains. It should not be used when other agents are hkely to be effective. Indiscriminant use and overuse will hasten selection of resistant strains and the evenmal loss of this valuable new agent. 

The first of a new class of antibiotics (oxazolidinones), linezolid is active against many drug-resistant gram-positive cocci, including strains resistant to beta-lactams and vancomycin (eg, vancomycin-resistant Enterococcus faecium). Linezolid binds to a unique site on the SOS ribosomal subunit, and there is currently no cross-resistance with other protein synthesis inhibitors. Linezolid is available in both oral and parenteral formulations. 

CarroU MW, Choi H, Min S, Hwang S, Park H, Song T, et al. Rhabdomyolysis in a patient treated with linezolid for extensively drug-resistant tuberculosis. Qin Infect Dis 2012 54(ll) 1624-7. 

Rose PC, Hallbauer UM, Seddon JA, HesseUng AC, Schaaf HS. Linezolid-containing regimens for the treatment of drug-resistant tuberculosis in South African children. Int J Tuberc Lung Dis 2012 16(12) 1588-93. 

B) Seek the newly approved drug linezolid for possibility of vancomycin-resistant enterococci (VRE)... 

Due to its novel mode of action, it is active against pathogens that have acquired resistance to existing drugs. Ranbezolid and eperezolid are stmcturally similar to linezolid only substitutions of the aromatic ring are different (Figure 8.22). 

Linezolid inhibits protein synthesis by preventing formation of the ribosome complex that initiates protein synthesis. Its unique binding site, located on 23S ribosomal RNA of the 50S subunit, results in no cross-resistance with other drug classes. Resistance is caused by mutation of the linezolid binding site on 23S ribosomal RNA. 

Linezolid Prevents bacterial protein synthesis by binding to the 23S ribosomal RNA of 50S subunit Bacteriostatic activity against susceptible bacteria Infections caused by methicillin-resistant staphylococci and vancomycin-resistant enterococci Oral, IV hepatic clearance (half-life 6 h) dosed twice-daily Toxicity Duration-dependent bone marrow suppression, neuropathy, and optic neuritis serotonin-syndrome may occur when coadministered with other serotonergic drugs (eg, selective serotonin reuptake inhibitors)... 

Linezolid inhibits protein synthesis by binding to the P site of the 508 ribosomal subunit and preventing formation of the larger ribosomal-fMet-tRNA complex that initiates protein synthesis. As mentioned above, there is no crossresistance with other drug classes. Resistance in enterococci and staphylococci is due to point mutations of the 238 rRNA. As multiple copies of 238 rRNA genes are present in bacteria, resistance generally requires mutations in two or more copies. 

Linezolid is approved for use in vancomycin-resistant enterococcal infections. There are very few alternatives available, and none of the other drugs listed are likely to be effective. The answer is (C). 

Quinupristin-dalfopristin and linezolid are newer drugs with activity against gram-positive cocci resistant to vancomycin and conventional antibiotics. 

Observational studies In a retrospective study in South Korea of linezolid in combination with other second-line drugs in 11 patients with intractable multidrug resistant tuberculosis, nine had serious adverse events [145 ]. Eight patients developed a peripheral neuropathy in the legs after a median of 4 months linezolid was withdrawn in these cases. Three patients developed an optic neuropathy, including two who had a peripheral neuropathy, after a median of 4 months. Two patients developed anemia requiring blood transfusion. 

---