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Linezolid: in infants and children with severe Gram-positive infections
Katherine A Lyseng-Williamson1, Karen L Goa
1Adis International Inc., Yardley, Pennsylvania 19067, USA. demail@adis.com
Abstract:
Linezolid is an oxazolidinone antibacterial agent that has inhibitory activity against a broad range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. The systemic clearance and, therefore, the area under the plasma concentration-time curve and elimination half-life of linezolid change with increasing age in pediatric patients. With the exception of pre-term neonates aged <1 week, systemic clearance is more rapid in pediatric patients aged 0-11 years than in adolescents. The pharmacokinetic profile of linezolid is similar in adolescents and adults. Linezolid was as effective as vancomycin in the treatment of pediatric patients with Gram-positive infections (clinical cure rate 89.3% vs 84.5%), and as effective as cefadroxil in the treatment of children and adolescents with Gram-positive uncomplicated skin and skin structure infections (91.0% vs 90.0%) in the clinically evaluable population of two randomized, comparator-controlled trials. The clinical cure rate with linezolid was 92.4% in a noncomparative trial in hospitalized pediatric patients with community-acquired pneumonia. All patients with proven pneumococcal pneumonia were considered cured. Linezolid is generally well tolerated. The most common drug-related adverse events in the comparator-controlled trials were diarrhea, nausea, and headache; most events were mild to moderate in severity.
Insights
Linezolid effectively treats Gram-positive infections in pediatric patients, showing comparable efficacy to vancomycin and cefadroxil. This antibacterial agent is generally well-tolerated, with mild side effects like diarrhea and nausea.
Area of Science:
- Infectious Diseases
- Pharmacology
- Pediatrics
Background:
- Linezolid is a crucial oxazolidinone antibiotic for Gram-positive bacterial infections.
- Pediatric pharmacokinetics of linezolid vary with age, differing from adult profiles.
- Key Gram-positive pathogens include MRSA, VRE, and penicillin-resistant S. pneumoniae.
Purpose of the Study:
- To evaluate the efficacy and safety of linezolid in pediatric patients.
- To compare linezolid's effectiveness against standard treatments like vancomycin and cefadroxil.
- To assess linezolid's pharmacokinetic profile across different pediatric age groups.
Main Methods:
- Two randomized, comparator-controlled trials were conducted.
- A noncomparative trial assessed linezolid for community-acquired pneumonia in hospitalized children.
- Efficacy was determined by clinical cure rates, comparing linezolid to vancomycin and cefadroxil.
Main Results:
- Linezolid demonstrated comparable efficacy to vancomycin (89.3% vs 84.5%) for Gram-positive infections.
- Effectiveness against uncomplicated skin infections was similar to cefadroxil (91.0% vs 90.0%).
- A 92.4% clinical cure rate was observed in pediatric patients with community-acquired pneumonia.
Conclusions:
- Linezolid is an effective treatment option for pediatric Gram-positive infections.
- The drug is generally well-tolerated, with mild adverse events reported.
- Pharmacokinetic differences in pediatric patients necessitate age-specific considerations.
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