March 2000
SEVILLE, SPAIN - The new streptogramin antibiotic quinupristin/dalfopristin (Synercid, Aventis) seems to be safe and effective in pediatric patients, according to a study reported here at the Fifth International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones.
The safety and efficacy data compare favorably to the adult experience. Ann M. Loeffler, MD, attending physician, division of infectious diseases, Children's Hospital, Oakland, CA, reviewed data from 63 children enrolled in the quinupristin/dalfopristin noncomparative compassionate use program.
Participants ranged from 2 weeks to 18 years of age, with 20 children younger than 2 years of age. All had at least one gram-positive infection resistant to all clinically appropriate antibiotics or were intolerant to or were failing treatment. Infections included bacteremia in 21 patients, intra-abdominal infection in 15, central catheter-related bacteremia in 13, skin and skin structure infections in four, and various other infections in 14. Some patients had more than one infection.
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The organisms included vancomycin-resistant Enterococcus faecium (VREF) in 48 patients, Enterococcus sp. in six patients, Staphylococcus epidermidis in six, Staphylococcus aureus in five, and Streptococcus pneumoniae in one. In this series, 62.7% of patients had severe underlying hematologic disorders, 44.1% had cardiovascular disorders, and 39% had undergone transplantation.
Quinupristin/dalfopristin was dosed at 7.5 mg/kg either every 12 hours or every eight hours. In all but four children, the drug was infused exclusively through a central venous catheter. Most patients had received another antibiotic at some time during the course of treatment.
The most frequently used antimicrobials included aminoglycosides, glycopeptide, cephalosporins, penicillins and chloramphenicol.
The overall treatment success rate (defined as a combination of the clinical and bacteriologic response rates) was 71%, Loeffler said. A 51.1% success rate has been reported in adults.
When patients were stratified by age (0-1 month, >1 month to 2 years, >2 years to 12 years, >12 years to 16 years, and >16 years to 18 years), efficacy was found to be comparable across all age groups.
Quinupristin/dalfopristin was generally well-tolerated. Nonvenous adverse events possibly or probably related to the study drug occurred in four (6.3%) children. The most frequent treatment-related adverse events were rash and pain, each occurring in two (3.2%) patients. The frequency of adverse events was similar for all age groups, and no patient had a drug-related clinical adverse event that required treatment to be stopped. Three children (4.8%) had abnormalities in laboratory values that necessitated withdrawal from treatment. Quinupristin/dalfopristin's overall safety profile was similar to that which has been observed in adults.
Twenty-six (41.3%) patients died, largely as a result of progression of their underlying disease.
"In this group of difficult-to-treat patients, many of whom had failed prior therapies, quinupristin/dalfopristin proved effective and well-tolerated," Loeffler said. "The results suggest that this antibiotic should be considered as a therapeutic option for the treatment of pediatric patients with gram-positive infection, including those caused by VREF and methicillin-resistant S. aureus (MRSA)."
Loeffler emphasized that more research is needed to examine the use of quinupristin/dalfopristin in children. While the present study looked at results in 63 of the 174 pediatric patients enrolled in the quinupristin/dalfopristin compassionate use program, data collection for the remaining 111 patients is presently underway.
The study was conducted at sites in the United States, United Kingdom, France and Israel.
For more information:
- Loeffler AM. Efficacy and safety of treatment of pediatric patients with quinupristin/dalfopristin. Poster Presentation 6.04. Presented at the Fifth International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones. Jan. 26-28, 2000. Seville, Spain.
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