| Table 1: | ||
|
Antibacterial
Agents
|
||
|
|
Linezolid
(Zyvox) |
Quinupristin/Dalfopristin
(Synercid)
|
| Mechanism of action | Binds to the 50S ribosome at a site that inhibits translation. | Binds to sequential sites on the 50S subunit of the ribosome |
| Mechanism of resistance | 23S ribosomal RNA mutations | Methylation of the 23S ribosome (mediated by the MLSb gene); active efflux (mef gene); enzyme degradation |
| Spectrum of activity | Enterococcus faecium, E faecalis; Staphylococcus aureus, coagulase-negative staphylococci; streptococci, including multidrug-resistant Streptococcus pneumoniae; Corynebacterium sp, Moraxella catarrhalis, Listeria monocytogenes, Pasteurella multocida, Bacteroides fragilis, and some rapidly growing Mycobacteria species | Enterococcus faecium; Staphylococcus aureus, coagulase-negative staphylococci; streptococci, including multidrug-resistant Streptococcus pneumoniae; Listeria monocytogenes, Moraxella catarrhalis, Corynebacterium jeikeium, Mycoplasma pneumoniae, Neisseria meningitidis, Fusobacterium sp, peptostreptococci, Clostridium perfringens |
| Oral absorption | 100% | None |
| Half-life | 4 h | Quinupristin + metabolites, 3 h; Dalfopristin + metabolites, 1 h |
| Metabolism | Oxidation, 2 inactive metabolites | Hepatic, 3 active metabolites (2 quinupristin, 1 dalfopristin) |
| Excretion | Renal 30% unchanged in the urine, metabolites also eliminated renally. | Biliary |
| Clinical side effects | Nausea, vomiting, diarrhea, headache | Arthralgia, myalgia; phlebitis; nausea |
| Laboratory abnormalities | Thrombocytopenia, leukopenia, anemia | Elevated bilirubin, abnormal liver function enzymes |
| Mechanism of drug interactions | Nonselective inhibitor of monoamine oxidase | Inhibits cytochrome P-450 3A4 enzyme pathway (not a substrate) |
| Potential drug interactions | Adrenergic and serotonergic agents | Cyclosporine, nifedipine, midazolam, terfenidine, protease inhibitors, HMG-CoA reductase inhibitors, other P-450 3A4 substrates |
| Other considerations | Incompatible with amphotericin B, chlorpromazine, diazepam, pentamidine, erythromycin, phenytoin, trimethoprim/sulfamethoxazole, ceftriaxone. | Incompatible with saline and heparin; IV lines should be flushed with D5W. |
| Approved indications |
|
|
| Usual dose | 600 mg PO or IV q12h (400 mg IV or PO q12h for uncomplicated skin/skin structure infections) |
5-7.5
mg/kg IV q8h
|
| HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; PO = oral; IV = intravenous; D5W = 5% dextrose in water; VRE = vancomycin-resistant enterococci | ||
|
Copyright
2002 The Cleveland Clinic Foundation
|
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