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Linezolid (Zyvox) is considered medically necessary for the treatment of infections caused by the following pathogens:

Vancomycin resistant Enterococcus faecium or Enterococcus faecalis

Methicillin resistant Staphylococcus aureus

Methicillin resistant Streptococcus pyogenes or Streptococcus agalactiae

Duration of therapy will be limited to 14 days including inpatient therapy.

Description:

Linezolid (Zyvox) is in a new class of synthetic antibiotics known as fluorinated oxazolidinones. Oxazolidinones exhibit a mechanism of action that is different from other antimicrobial classes. The predominant activity of Linezolid is against aerobic gram-positive organisms. Linezolid exhibits little activity against aerobic gram-negative organisms or anaerobes in vitro; combination with other antimicrobial therapies may be clinically indicated if presumptive or documented pathogens include gram-negative or anaerobic bacteria.

Linezolid (Zyvox) is a reversible, non-selective inhibitor of monoamine oxidase (MAO) which increases the potential for drug interactions and medication safety issues.

Linezolid (Zyvox) Dosage:

For the treatment of the following infections due to susceptible organism(s) including those infections with concurrent bacteremia or pneumonia:
NOTE: Due to inappropriate use and increasing resistant organisms, consider treatment alternatives prior to using Linezolid in the outpatient setting. Duration of Linezolid treatment is determined by site and severity of the infection and clinical response. In clinical trials, treatment duration ranged from 7-28 days.
- for infections due to Vancomycin-resistant enterococci (VRE) (i.e., E. faecium; E. faecalis) at any site, including those infections with concurrent bacteremia or pneumonia:
Oral dosage (tablets or oral suspension):
Adults and adolescents>= 12 years: 600 mg PO every 12 hours for 14-28 days. May give aztreonam or aminoglycosides concurrently if indicated.
Children, infants, and term neonates from birth to 11 years: 10 mg/kg PO every 8 hours for 14-28 days.
Pre-term neonates < 7 days old (gestational age < 34 weeks): 10 mg/kg PO every 12 hours for 10-14 days. Consideration may be given to the use of 10 mg/kg every 8 hours in those with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg PO every 8 hours by 7 days of life.
Intravenous infusion dosage:
Adults and adolescents >= 12 years: 600 mg IV every 12 hours for 14-28 days. May give aztreonam or aminoglycosides concurrently if indicated.
Children, infants, and term neonates from birth to 11 years: 10 mg/kg IV every 8 hours for 14-28 days. Linezolid for the empiric treatment of pediatric patients with central nervous system infections is not recommended. Pediatric patients exhibit variability in drug clearance and systemic exposure. Pediatric patients with ventriculoperitoneal shunts obtained variable cerebrospinal fluid (CSF) Linezolid concentrations and therapeutic concentrations were not consistently achieved or maintained in the CSF.
Pre-term neonates < 7 days old (gestational age < 34 weeks): 10 mg/kg IV every 12 hours for 10-14 days. Consideration may be given to the use of 10 mg/kg every 8 hours in those with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg IV every 8 hours by 7 days of life.
- for nosocomial or community-acquired pneumonia infections due to susceptible organisms, including those pneumonias with concurrent bacteremia:
Oral dosage (tablets or oral suspension):
Adults and adolescents>= 12 years: 600 mg PO every 12 hours for 10-14 days.
Children, infants, and term neonates from birth to 11 years: 10 mg/kg PO every 8 hours for 10-14 days.
Pre-term neonates < 7 days old (gestational age < 34 weeks): 10 mg/kg PO every 12 hours for 10-14 days. Consideration may be given to the use of 10 mg/kg every 8 hours in those with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg PO every 8 hours by 7 days of life.
Intravenous infusion dosage:
Adults and adolescents >= 12 years: 600 mg IV every 12 hours for 10-14 days.
Children, infants, and term neonates from birth to 11 years: 10 mg/kg IV every 8 hours for 10-14 days.
Pre-term neonates < 7 days old (gestational age < 34 weeks): 10 mg/kg IV every 12 hours for 10-14 days. Consideration may be given to the use of 10 mg/kg every 8 hours in those with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg IV every 8 hours by 7 days of life.

For the treatment of skin and skin structure infections due to susceptible organisms:
NOTE: Due to inappropriate use and increasing resistant organisms, consider treatment alternatives prior to using Linezolid in the outpatient setting. Duration of Linezolid treatment is determined by site and severity of the infection and clinical response. In clinical trials, treatment duration ranged 7-28 days.
for the treatment of complicated skin and skin structure infections including diabetic foot infections (e.g., diabetic foot ulcer) without concomitant osteomyelitis:
Oral dosage (tablets or oral suspension):
Adults and adolescents >= 12 years: 600 mg PO every 12 hours for 10-14 days. NOTE: Linezolid has not been studied for decubital ulcers.
Children, infants, and term neonates from birth to 11 years: 10 mg/kg PO every 8 hours for 10-14 consecutive days.
Pre-term neonates < 7 days old (gestational age < 34 weeks): 10 mg/kg PO every 12 hours for 10-14 consecutive days. Consideration may be given to the use of 10 mg/kg every 8 hours in those with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg PO every 8 hours by 7 days of life.
Intravenous infusion dosage:
Adults and adolescents >= 12 years: 600 mg IV every 12 hours for 10-14 days. NOTE: Linezolid has not been studied for decubital ulcers.
Children, infants, and term neonates from birth to 11 years: 10 mg/kg IV every 8 hours for 10-14 consecutive days.
Pre-term neonates < 7 days old (gestational age < 34 weeks): 10 mg/kg IV every 12 hours for 10-14 consecutive days. Consideration may be given to the use of 10 mg/kg every 8 hours in those with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg IV every 8 hours by 7 days of life.
for the treatment of uncomplicated skin and skin structure infections:
Oral dosage (tablets or oral suspension):
Adults: 400 mg PO every 12 hours for 10-14 days.
Adolescents >= 12 years: 600 mg PO every 12 hours for 10-14 days.
Children 5-11 years: 10 mg/kg PO every 12 hours for 10-14 days.
Children, infants, and term neonates from birth to < 5 years: 10 mg/kg PO every 8 hours for 10-14 days.
Pre-term neonates < 7 days old (gestational age < 34 weeks): 10 mg/kg PO every 12 hours for 10-14 days. Consideration may be given to the use of 10 mg/kg every 8 hours in those with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg PO every 8 hours by 7 days of life.

The most commonly reported adverse events include diarrhea, headache, nausea and vomiting. Because Linezolid (Zyvox) is a nonselective inhibitor of monoamine oxidase (MAO), it may increase systolic blood pressure due to the presence of higher levels of circulating endogenous catecholamines (e.g., norepinephrine).

Linezolid (Zyvox) is pregnancy category c.

References:

Gonzales RD, PC Schreckenberger, MB Graham, et al. Infections due to vancomycin-resistant Enterococcus faecium resistant to Linezolid. The Lancet 2001; 357:1179.

Herrero IA, NC Issa, R Patel. Nosocomial spread of Linezolid-resistant, vancomycin-resistant Enterococcus faecium. The New England Journal of Medicine 2002; 346:867-869.