19th March 2015: William A. “Bill” Craig, MD, died peacefully at University of Wisconsin (UW) Hospital surrounded by his beloved family, 11 Mar 2015, at age 75.
Bill was born in Arkansas City, KS, on 28 Nov, 1939, and graduated from Wayland Academy, Beaver Dam, WI in 1957; Haverford College, PA in 1961; and Tufts Medical School (Alpha Omega Alpha), Boston, MA in 1965.
He joined the UW faculty in 1973, as a founding member of the new infectious disease division. Appointed jointly at the Madison VA Hospital, he served as Chief of Infectious Diseases and Associate Chief of Staff for Education at the VA; he was also Program Director for the UW Internal Medicine Residency. He was central to the application of the then emerging subject of pharmacokinetics and pharmacodynamics (PK/PD) for antimicrobial drugs. This was to mark the start of his impact on medical science, and he became integral to the development of new antibiotics over the next four decades. His legacy allows early understanding of whether new antibiotics are likely to work in humans and, as bacterial resistance has become one of Society’s greatest challenges in the last part of the 20th Century, these PK/PD tools rapidly speed research and development.
Bill published around 200 manuscripts and is best known for his landmark research into appropriate dosing of several antibiotic classes, most notably β-lactams with his 1992 paper opening the way for continuous infusion regimen of these drugs. Bill’s studies of post-antibiotic effects and the modelling of human pharmacokinetics in a range of animal models enhanced our understanding of a difficult concept.
It was during this period that Bill’s insightful and creative ways came to the fore, as both regulators and pharmaceutical developers addressed the highly contentious issue of antibiotic development. It was under Bill’s quiet but determined mentorship that the BSAC, IDSA & FDA collectively instituted a sea-change in the regulatory processes. These changes addressed the integration of basic in vitro microbiology with the growing knowledge of clinical pharmacokinetics which laid the pathway to our current position. Indeed, towards the end of the last century, perhaps one of his most referenced works was his 1998 rationale for PK-PD: in Mice and Men(1), which really encapsulated our then current knowledge of how antibiotics work in in vivo models and can be used to better guide our dosing in humans.
More recently, Bill and colleagues have been asking searching questions on the effects of inoculum and other clinically relevant factors on outcomes, in particular the selection of resistant strains. Even in 2014 Bill was still pushing the boundaries, asking “are blood concentrations enough to establish PK-PD relationships”?
He constantly enquired, “do we really know what is the best dose in the current clinical situation, as well as for preserving antibiotics?”
Throughout his career, one of the striking features of Bill’s influence on modern antibiotic development was his humble but incisive approach to questioning and then gently directing antibiotic development. His incredible diligence, thoroughness and passion for developing new methods of dosing antibiotics, and for testing development of new antibiotics, was recognized by the Garrod Medal from the British Society for Antimicrobial Chemotherapy, the Hamoa Umezawa Award from the International Society of Chemotherapy, the Bristol Award from the Infectious Diseases Society of America, The Paul Ehrlich Magic-Bullet Lifetime Achievement Award, and the Sanofi-Aventis Award from the American Academy of Microbiology. In 2011, he was honored to receive The Haverford Award for Service to Humanity. He relished the 6 years he spent on the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) serving as a committee member, vice chair, and chair.
We will miss Bill’s gracious presence and insight in an increasingly complicated world.