• Linezolid shows good activity against S.
aureus which is generally equivalent to that of vancomycin.
S. epidermidis and S. haemolyticus have similar
suscepti-bilities to linezolid and vancomycin.
• Linezolid is highly effective against
penicillin resistant streptococcus pneumoniae.
Additionally, linezolid remains active against strains of
pneumococci resistant to ceftriaxone, erythromycin, clindamycin
and tetracycline.
• Linezolid has activity against all
enterococcal isolates tested, regardless of vancomycin
resistance pattern.
• Linezolid has potent activity against other
gram-positive organisms including S. pyogenes, Bacillus spp.,
Corynebacterium spp., Listeria monocytogenes,
Myco-bacterium tuberculosis and Rhodococcus spp.
Gram negative bacteria
Linezolid lacks significant effects against most
gram negative pathogens but have in vitro activity against
Moraxella catarrhalis, Haemophilus influenzae,
Legionella spp., Neisseria gonorrhoae and Bordetella
pertussis. Pseudomonas aeroginosa and enterobacteriaceae
including E. coli, Kleb-siella pneumoniae and
Proteus are not susceptible to Linezolid.
Anaerobes
Linezolid demonstrated similar activity as
vancomycin against Clostridium difficile and C. perfringes.
Additionally, linezolid has good activity against gram negative
anaerobes including Bacteriodes spp., Fusobacterium
nucleatum and Prevotella spp.
Therapeutic uses
US Food and Drug Administration (FDA) has
approved linezolid for the treatment of gram positive infection in
infants and children.
Linezolid is an excellent alternative to
vancomycin for the treatment of nosocomial pneumonia caused by
methicillin resistant Staphylococcus aureus, including
ventilator associated pneumonia(6,7). Linezolid is also a cost
effective alternative to vancomycin for the treatment of ventilator
associated pneu-monia (8). In 1 year to 17-year-old children with
community acquired pneumonia, Linezolid was well tolerated and could
be considered alternative to vancomycin for serious infection caused
by antibiotic resistant gram positive cocci(9).
Clinical success rates exceeding 89% were
observed in adult patients with complicated and uncomplicated
skin/soft tissue infections(10). Linezolid also exhibited similar
efficacy to oxacillin / dicloxacillin and vancomycin(11).
Linezolid has shown good CSF penetra-tion and
thus seems a promising candidate for treatment of CNS
infections(12). Intravenous linezolid appears to be safe and
effective therapy for vancomycin resistant entero-coccus
meningitis(13,14).
Linezolid should be reserved as an agent of last
resort for treatment of infections caused by multiple drug resistant
strains. It should not be used when alternative agents are likely to
be effective. Indiscriminate use and overuse will hasten selection
of resistant strains and the eventual loss of this valuable new
agent.
Adverse effects
The drug seems to be well tolerated, with
generally minor side effects. Drug related adverse events occurred
in 32.7% of patients, were generally mild to moderate intensity,
resolved during continuous linezolid treatment, and were not
dose-related. The most commonly occurring drug related adverse
events were nausea (5.4%), diarrhea (5.2%), tongue discoloration
(2.5%), oral moniliasis (2.3%), taste perversion (2.3%) and headache
(2.3%). Thrombocytopenia or a significant reduction in platelet
count has been associated with linezolid. The reported incidence is
2.4% and its occurrence is related to duration of therapy.
Myelosuppression (including anemia, leukopenia,
pancytopenia, and thrombo-cytopenia) has been reported in patients
receiving linezolid but when linezolid was discontinued, the
affected hematologic parameters rise towards pretreatment levels.
Weekly monitoring of complete blood count should be done in patients
who receive linezolid, particularly in those who receive linezolid
for longer than 2 weeks, those with preexisting myelosuppression,
those receiving concomitant drugs that produce bone marrow
suppression, or those with a chronic infection who have received
previous or concomitant antibiotic therapy. Linezolid should be
discontinued in patients who develop or have worsening
myelosuppression. People who are at increased risk of bleeding
disorders or have low platelets should get their platelet count
monitoring during linezolid treatment. Recurrent nausea and vomiting
due to lactic acidosis has been reported with the use of linezolid.
In patients who present with diarrhea subsequent to administration
of linezolid possibility of pseudomembranous colitis should be
considered as with all antibacterial agents.
Linezolid is a reversible, nonselective inhibitor
of monoamine oxidase (MAO), and a potential interaction with
adrenergic or serotonergic agents is possible. Patients should avoid
consuming food or beverages containing tyramine since pressor
response was observed when administered with tyramine. Dopamine,
epinephrine or decongestants containing pseudoephedrine may also
produce an exaggerated pressor response. Careful dosing titration is
recommended when initiating dopamine or epinephrine.
Several incompatibilities have been reported on
coadministration with amphotericin B, ceftriaxone, chlorpromazine,
diazepam, erythromycin, phenytoin, and
trimethoprim-sulfamethoxazole(11).
Disease interactions
Caution is advised if one has a history of high
blood pressure, hyperthyroidism, pheochromocytoma, carcinoid
syndrome, thrombocytopenia or other bleeding disorders, diarrhea, or
decreased kidney function.
Over dosage
In the event of over dosage, supportive care is
advised with maintenance of glomerular filtration. Hemodialysis may
facilitate more rapid elimination of Linezolid.
Dosage and administration
Oral and parentral dosage forms:
• Children - 10 mg/kg every 12 hours.
• Adults - 600 mg every 12 hours.
The duration of treatment for most of the
infections like pneumonia including community acquired pneumonia and
skin infections is 10-14 days. It is advised to give therapy for
14-28 days in Vancomycin resistant enterococcal infections.
Linezolid is available as tablets containing 600
mg (linospan, lizomed, linox, lizbid), as injections of 100 mL and
300 mL containing 2 mg/mL (linospan, linox IV) and oral suspension
(20 mg/mL). Cost of a tablet is Rs. 75-100 and 100 ml injection is
Rs. 150-200.
IV administration: IV administration of drug
should be done over 30-120 min.
Pregnant and lactating mothers: Adequate
human studies have not been done in pregnant and lactating females
so risk and benefits of using this drug should be considered
individually.
