Pharmacia Corporation announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application (sNDA) of Zyvox (linezolid injection, tablets and for oral suspension) for the treatment of Gram-positive infections in infants and children, which include complicated skin and skin structure infections and nosocomial (hospital-acquired) pneumonia. These infections are increasingly caused by resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and are becoming a significant health threat to children and infants both within and outside the hospital. The FDA approval for Zyvox also included the treatment of community-acquired pneumonia, uncomplicated skin and skin structure infections and vancomycin-resistant Enterococci faecium (VREF) in infants and children.
Zyvox was approved for use in adults in the U.S. in April 2000. This novel antibiotic has fully bioavailable IV and oral formulations that provide dosing convenience for physicians and patients, allowing some patients to return home on the oral form at the earliest appropriate point.
"The incidence of difficult-to-treat Gram-positive infections is increasing at an alarming rate in children, especially in those without typical risk factors such as recent hospitalization," said Sheldon Kaplan, Baylor College of Medicine professor of pediatrics and chief of the infectious disease service at Texas Children's Hospital. "The approval of Zyvox in this population is a tremendous advance for the medical community, providing a new, effective and well-tolerated option for infants and children with certain serious infections."
A clinical study submitted to the FDA has shown that Zyvox is well-tolerated and as effective as vancomycin in children, ranging from birth to 11 years of age, with known or suspected resistant Gram-positive infections. In addition to the approved indications, the product also was tested in children with catheter-related bacteremia and bacteremia of an unknown source, caused by resistant Gram-positive bacteria including MRSA. Clinical studies submitted to the FDA involved approximately 1,100 children. Limited clinical experience in pediatric patients suggests efficacy is similar to that in adults. The safety and effectiveness of Zyvox for the treatment of pediatric patients are supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic data in pediatric patients, and additional data from comparator-controlled studies of Gram-positive infections in pediatric patients ranging in age from birth through 17 years. Most frequently reported adverse events in pediatric patients were fever, diarrhea and vomiting.
"The approval of Zyvox for use in children is important because there are limited proven options available to treat MRSA in this vulnerable population," said Ferdinand E. Massari, vice president of clinical research for infectious diseases and urology at Pharmacia Corporation. "An effective and well-tolerated treatment is especially important for the youngest patients."
Zyvox comes from the first new class of antibiotics -- the oxazolidinones -- to be introduced in 35 years. It has a completely novel mechanism of action that stops bacterial protein production at the beginning of the process. Without protein production, bacteria cannot multiply.
Zyvox also is indicated for the treatment of adults with susceptible and resistant strains of designated organisms, including patients with nosocomial pneumonia and complicated skin and skin structure infections caused by MRSA infections and infections caused by VREF.
Patients receiving linezolid should have complete blood counts monitored weekly, since myelosuppression has been reported. This applies particularly to those who: receive Zyvox for longer than two weeks; have pre-existing myelosuppression; are receiving concomitant drugs that produce bone marrow suppression; or have a chronic infection and have received previous or concomitant antibiotic therapy.
MRSA has traditionally been viewed as a pathogen that causes life-threatening hospital-acquired infections. Currently in the U.S., more than 50 percent of Staph strains causing adult infections in hospital intensive care units are resistant to methicillin treatment, and in other hospital settings more than 40 percent of Staph infections are caused by MRSA. In addition, over the past five years it has increasingly been recognized as a threat in the community, particularly in children. According to recent reports at Texas Children's Hospital, more than 60 per cent of the children treated at the hospital with Staphylococcus aureus (S. aureus) infections have a methicillin-resistant isolate (MRSA). This problem is very serious, as many children have never been exposed to these bacteria prior to entering the hospital, a typical risk factor found in adult populations. This underscores the need for novel treatment options for both adults and children with Gram- positive infections, including those caused by resistant organisms.