A Historical Perspective on Pharmacological Studies of Gentamicin for Therapy of Neonatal Meningitis

Abstract

Address correspondence to: George H. McCracken, Jr., MD, UT Southwestern Medical Center, Dallas, Department of Pediatrics, Division of Infectious Diseases, 5323 Harry Hines Blvd., F3-202, Dallas, TX 75390-9063, email: george.mccracken@utsouthwestern.edu © 2006 Pediatric Pharmacy Advocacy Group ABBREVIATIONS CSF, cerebral spinal fluid; IL-1β, interleukin-1 beta; LPS, lipopolysaccharide; MIC, minimal inhibitory concentration; PPRU, Pediatric Pharmacology Research Unit Much of my early career in Pediatric Infectious Disease was devoted to defining the optimal management of neonatal meningitis caused by Gram negative enteric bacteria. To accomplish this required an understanding of clinical pharmacology of antibiotics in newborn infants, an area rarely explored in the period before the late 1960s when I started my investigative career. Indeed, in 1968 Dr. Harry Shirkey, a pharmacist-turned-pediatrician, lamented the fact that infants and children were often denied use of many drugs because of the lack of data on their pharmacokinetics, safety and efficacy.1 He termed these patients “therapeutic orphans” and encouraged the development of active programs of clinical pharmacology and drug testing in pediatric patients, especially in infants and young children. It was in this setting that I launched my investigations of the clinical pharmacology of antibiotics in newborn and young infants, particularly as they pertained to treatment of bacterial meningitis. Now, 38 years later, I am thrilled to receive the Sumner J. Yaffe Lifetime Achievement Award in Pediatric Pharmacology and Therapeutics from the Pediatric Pharmacy Advocacy Group in recognition of these and other studies that helped to clarify the safe and effective use of antibiotics in infants and children. I am honored to receive this award named for Dr. Yaffe, who was as instrumental as anyone in promoting the critical impor-