Linezolid (Zyvox) is a synthetic
oxazolidinone antimicrobial agent that is used in the treatment of infections
caused by aerobic Gram-positive bacteria. Linezolid works be inhibiting
bacterial protein synthesis by binding to a site on the bacterial 23S ribosomal
RNA of the 50S subunit. This ultimately prevents the formation of a functional
70S initiation complex, which is an essential component of the bacterial
translation process during protein synthesis. As it relates to its
antimicrobial activity, linezolid has been shown to be both bacteriostatic
against enterococcus and staphylococci and bactericidal against streptococci.
Unfortunately, one reported complication of linezolid therapy is the potential
for myelosuppression. According to the package insert,
Linezolid-associated thrombocytopenia is thought to be dependent on duration of
therapy (greater than 2 weeks of treatment).
Thrombocytopenia
induced by linezolid is thought to occur via a mechanism similar to that of
quinine/quinidine-induced immune-mediated platelet destruction. In this
scenario, the drug or metabolite binds to platelet membrane glycoprotein
IIb/IIIa, which then acts as an antigen to the immune system. When this
occurs, the Fab portion of immunoglobulin G (IgG) antibodies binds to this
complex on the platelet surface. The Fc portion of that IgG antibody
bound to the platelet surface then binds to macrophages, when then attack the
platelet and clear it from the circulation. This mechanism has been suggested
due to the absence of heparin-induced thrombocytopenia (HIT) antibodies or
other features of heparin-induced thrombocytopenia/thrombosis (HITT) syndrome,
the presence of adequate megakaryocytes in the marrow, and improvement in the
rate of decline of platelet count in response to intravenous immune globulin
(IVIG) therapy. Furthermore, if IVIG is given in this situation it can
slow platelet destruction through a blocking of the Fc receptors of the
antibodies bond to the platelet surface.
While
the product package insert makes this claim, there is evidence to suggest that
this may not linked to the duration of linezolid exposure.
References:
- Bernstein WB, Trotta RF, Rector JT, et al. Mechanisms
for linezolid-induced anemia and thrombocytopenia. Ann Pharmacother
2003;37:517-20.
- Garazzino S, Guiseppe De Rosa F, Bargiacchi O, et al.
Haematological safety of long-term therapy with linezolid. Int J
Antimicrob Agents 2007;29:480-3.
