Gram daptomycin, linezolid, ceftaroline, telavancin and tigecycline.[2, 3]

Gram positive organisms including
staphylococcus aureus, coagulase-negative staphylococcus, streptococcus and
enterococcus account for a large percentage of infections in ICU. 1 They can
cause a variety of infections with different severities such as complicated and
uncomplicated skin and soft tissue infections, community or hospital acquired
pneumonia, meningitis, infective endocarditis and sepsis.

Drug resistant bacterial infections
have become clinical problem especially those associated with
methicillin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant
enterococcus (VRE) due to limited drugs available for treatment of those kinds
of infections. Consequently, that arise a problem until other drugs were
developed to be used instead of vancomycin for MRSA and VRE infections such as
daptomycin, linezolid, ceftaroline, telavancin and tigecycline.2, 3

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Linezolid is the first synthetic
oxazolidinone approved for use in 2000. It is a
bacteriostatic antibiotic against most organisms which inhibits bacterial
protein synthesis at early stage. Additionally, it blocks bacterial toxin
production such as Panton-Valentine leukocidin, alpha-hemolysin, and toxic
shock syndrome toxin-1. 2, 4 Moreover, it has spectrum of activity that
include gram positive organisms, anaerobic gram
negative, mycobacteria and nocardia. Thus, it has a clinical importance
due to its coverage for MRSA and VRE. Linezolid has been approved for use in
nosocomial and community acquired pneumonia in addition to skin and soft tissue
infections. 5

Thrombocytopenia defined as platelet
count <150,000/microL for adults. However, this definition should be interpreted according to each patient clinical course. In ICU, thrombocytopenia could be caused by number of mechanisms such as (1) hemodilution through massive fluid resuscitation (2) increased platelet consumption due to massive tissue trauma, bleeding, sepsis, or disseminated intravascular coagulation (DIC), and extracorporeal circuits, (3) decreased platelet production in the bone marrow which can also decrease white blood cells and red blood cells causing pancytopenia, (4) increased platelet sequestration in the spleen, and (5) platelet destruction by antibodies.6 In critically ill patients, thrombocytopenia may indicate an increased bleeding risk, but in some patients it can also indicate an increased risk for thrombosis. 6 Platelet transfusions sometimes are necessary in bleeding, but they can rarely cause side effects including allergic reactions, pathogen transmission, transfusion-related acute lung injury, 7 and increase the risk of venous thromboembolism. 8 This must be balanced against the bleeding risk. One of the major adverse effects reported of linezolid is myelosuppression. It could supress bone marrow production of leukocytes and platelets. However, these hematologic abnormalities were consistent with mild, reversible, duration-dependent myelosuppression. 9 Linezolid-induced thrombocytopenia is the most common reported hematologic abnormality. 5, 10 It was observed that thrombocytopenia can occur with prolonged duration of linezolid therapy (i.e. >2 weeks). 5
Other risk factors suggested to be associated with thrombocytopenia include
renal insufficiency, 11 dose escalation, 12 and chronic liver disease. 13
In Natsumoto B
et al study, 14 they reported that thrombocytopenia was significantly associated
with high daily dose per weight of linezolid and elevated serum creatinine.

On the other hand, there are several causes
that can be associated with thrombocytopenia in acutely ill or hospitalized
patients which can be wrongly misinterpreted as linezolid-associated thrombocytopenia.
For instance, it can be resulted of underlying illness such as sepsis, acute
infection, and DIC. 6 Therefore, it is suggested
in clinical practice to study each case independently to identify risk factors and
severity of decreased platelet count, and outweigh benefits and risks for drugs
suspected to cause thrombocytopenia.


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