An Overview of the NICHD/BPCA Meropenem in Infants Study

Studying the safety, efficacy, and dosing of meropenem for the treatment of complicated intra-abdominal infections in infants.

Summary

Meropenem is a broad-spectrum anti-microbial drug used to treat intra-abdominal infections in young infants. Intra-abdominal infections are common in premature infants younger than three months of age and are often fatal. Meropenem, which effectively treats many types of bacterial infections, is approved for use in adults and older children and has long been prescribed for infants younger than three months despite a lack of data about the effects of the drug on these patients.

Brian Smith, MD, MPH, MHS, of the Duke Clinical Research Institute, presents the NICHD/BPCA meropenem study.

The purpose of the meropenem study, which began in the summer of 2008, was to determine the optimal dosing regimen for meropenem in infants younger than 90 days old. Researchers were also interested in determining how safe the drug is for very young infants, especially when compared with imipenem, another broad-spectrum anti-microbial drug closely related to meropenem.

“Seizures are a known side effect [of imipenem], so we were particularly interested in looking to see if seizures were an adverse event we would see in this trial,” Smith said.

Testing young children presented certain challenges to researchers. Infants cannot provide biological specimens in the quantities that adults can. Only recently, Smith said, has medical technology allowed researchers to conduct studies using minute amounts of blood and other specimens.

“The blood samples that we used to measure the meropenem were very small,” he said. “They were 200 microliters, which is one-twenty-fifth of a teaspoon. We now have techniques that can measure concentrations of drugs in very small samples that weren’t available 20 or 30 years ago.”

The trial comprised 200 infants at 24 neonatal intensive care units across the United States. Each patient was given a dose of meropenem based on his or her gestational age at the time of birth and postnatal age at the time of the study. Researchers acquired blood samples from each infant when blood was being sampled as part of the children’s regular care.

Their findings suggested that meropenem as dosed in the study is a safe alternative for young infants with intra-abdominal infections. With this information in hand, researchers traveled to Washington, DC in November to suggest new labeling guidelines to the Food and Drug Administration. The agency has six months to make a decision about the proposed changes.

Daniel K. Benjamin, Jr., MD, PhD, MPH, professor of pediatrics at Duke, faculty associate director of the DCRI, and program director for pediatrics with the Duke Clinical Research Unit, served as principal investigator for the study. Benjamin; P. Brian Smith, MD, MPH, MHS, and Michael Cohen-Wolkowiez, MD, published their initial findings in the October 2011 issue of the Pediatric Infectious Disease Journal.

Publications

Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra-abdominal infections
Smith PB, Cohen-Wolkowiez M, Castro LM, Poindexter B, Bidegain M, Weitkamp JH, Schelonka RL, Ward RM, Wade K, Valencia G, Burchfield D, Arrieta A, Bhatt-Mehta V, Walsh M, Kantak A, Rasmussen M, Sullivan JE, Finer N, Brozanski BS, Sanchez P, van den Anker J, Blumer J, Kearns GL, Capparelli EV, Anand R, Benjamin DK Jr; Meropenem Study Team.
The Pediatric Infectious Disease Journal • Volume 30, Number 10, October 2011, Page 844-849.
PubMed Central (PMC) ID: PMC3173561 [Free access]

Adverse events associated with meropenem versus imipenem/cilastatin therapy in a large retrospective cohort of hospitalized infants.
Hornik CP, Herring AH, Benjamin DK Jr, Capparelli EV, Kearns GL, van den Anker J, Cohen-Wolkowiez M, Clark RH, Smith PB; Best Pharmaceuticals for Children Act-Pediatric Trials Network.
Pediatric Infectious Diseases Journal • July 2013, volume 32, issue 7, pages 748-753.
PMCID: PMC3708263 [Free PMC article]

Safety and effectiveness of meropenem in infants with suspected or complicated intra-abdominal infections.
Cohen-Wolkowiez M, Poindexter B, Bidegain M, Weitkamp JH, Schelonka RL, Randolph DA, Ward RM, Wade K, Valencia G, Burchfield D, Arrieta A, Mehta V, Walsh M, Kantak A, Rasmussen M, Sullivan JE, Finer N, Rich W, Brozanski BS, van den Anker J, Blumer J, Laughon M, Watt KM, Kearns GL, Capparelli EV, Martz K, Berezny K, Benjamin DK Jr, Smith PB; on behalf of the Meropenem Study Team.
Clinical Infectious Disease • December 2012, volume 55, number 11, pages 1495-1502.
PMCID: PMC3491861 [Free PMC article]

OVERVIEW

Status:
Published; clinical study report submitted to FDA

ClinicalTrials.gov identifier:
NCT00621192

Principal Investigators: P. Brian Smith, MD, MPH, MHS and Daniel K. Benjamin, MD, PhD, MPH
Duke Health, Durham, NC

NEWS

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  • Meropenem label changed to reflect PTN findings March 24, 2015 The FDA recently changed the label for the drug meropenem to reflect findings from a study conducted by PTN investigators. Results from the study were published in the Pediatric Infectious Disease Journal.
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