August 1996
WILMINGTON, Del. — With the Food and Drug Administration's recent approval of meropenem, pediatricians have a potent new antibiotic at their disposal for treating bacterial meningitis and other serious infections.
Meropenem, which is marketed as Merrem by Zeneca Pharmaceuticals, based here, belongs to a class of compounds called carbapenems, which are the newest class of beta-lactam antibiotics. Meropenem is the first carbapenem antibiotic approved for use in children in the United States. The FDA approved the antibiotic, which is administered intravenously, as treatment for pediatric bacterial meningitis and complicated intra-abdominal infections in children and adults. Researchers have established the safety and efficacy of meropenem for children age 3 months and older, according to Zeneca officials.
Like other beta-lactam antibiotics, carbapenems inhibit bacterial reproduction by interfering with the formation of bacterial cell walls. Meropenem penetrates brain and spinal cord tissue and attacks a broad range of gram-negative and gram-positive bacteria.
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"There is a niche that it [meropenem] potentially will fill," said Jeffrey Blumer, MD, professor of pediatrics and pharmacology at Case Western Reserve School of Medicine, Cleveland. There may be a place for meropenem as a first-line empiric treatment for serious infections because meropenem is active against most pathogens that pediatricians encounter, Blumer said.
"This drug is going to be used primarily for serious infectious diseases in a hospital setting, not as an outpatient antibiotic," said Michael Scheld, MD, who is a professor of medicine at the University of Virginia School of Medicine, Charlottesville.
Meropenem's spectrum of antibacterial activity is similar to that of imipenem, the only other FDA-approved carbapenem. Imipenem is not indicated for use in children. Unlike meropenem, however, imipenem is associated with a higher rate of epileptic seizures and cannot be used to treat infections of the central nervous system, Scheld said. In addition, meropenem is not metabolized in the kidney by dehydropeptidase and, therefore, does not have to be given with a dehydropeptidase inhibitor, as is the case with imipenem.
Meropenem may be particularly useful in places with a high prevalence of drug-resistant pneumococci, said Blumer, who also is chief of the division of pediatric pharmacology and critical care at Rainbow Babies and Children's Hospital, Cleveland.
Scheld also believes that meropenem could be an important addition to the drug arsenal. "As we see increasing resistance among pneumococci to penicillin and third-generation cephalosporins, we need alternatives to treat serious bacterial infections, particularly meningitis."
It is not known whether meropenem will be more cost effective than conventional treatments such as ceftriaxone plus vancomycin, which is commonly used as empiric therapy for meningitis. "The jury's still out on that," Blumer said.
Clinical trials have shown that meropenem is as effective as cefotaxime in treating bacterial meningitis. In four clinical trials involving 456 children with bacterial meningitis, investigators randomly assigned 225 children to receive meropenem, 187 to receive cefotaxime and 34 to receive ceftriaxone. Of the clinically evaluable patients, investigators considered 78% of patients who received meropenem and 77% who received a comparison drug to be clinically cured. Each treatment arm had a comparable proportion of clinically evaluable patients and a similar distribution of pathogens cultured from cerebrospinal fluid.
Patients have tolerated meropenem well in clinical trials, according to investigators. Diarrhea, rash and vomiting were the most frequent adverse reactions that investigators reported as possibly, probably or definitely related to meropenem in 417 children treated for serious bacterial infections with 10 mg/kg to 40 mg/kg doses every eight hours. Diarrhea occurred in 4.3%, rash in 1.4% and vomiting in 1%, according to investigators. Among 198 children treated for meningitis with 40 mg/kg doses every eight hours, adverse reactions reported to be related to meropenem included rash and diarrhea, both of which occurred in 3.5% of patients; oral moniliasis, which occurred in 2%; and glossitis, which occurred in 1%.
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