Antimicrobial Resistance in the 21st Century / Emerging Infectious Diseases of the 21st Century (PDF)

consulting company. During his consulting years, he contributed significantly to the development of avibactam, eravacycline, and lefamulin. During his working career, he lived in Paris, France for several years. Although Dr. Shlaes has retired from Anti-infectives Consulting, he remains an Editor for the journal Antimicrobial Agents and Chemotherapy, writes a blog - Antibiotics - The Perfect Storm - and continues to be active in antibiotic policy making.



Karl Drlica is a molecular biologist (Ph.D. University of California, Berkeley) whose early work focused on DNA gyrase and the control of DNA supercoiling. His studies contributed to the discovery that bacterial supercoiling is homeostatically regulated by topoisomerases having opposing activities and that environmental conditions (oxygen tension, salt concentrations) can alter global supercoiling levels. Thus, bacterial chromosome structure is sensitive to conditions outside the cell. The finding by his laboratory that transcription can alter supercoiling opened studies on local control of supercoiling. In the 1990s, when immunosuppressed patients in New York City suffered an outbreak of multidrug-resistant tuberculosis, Drlica shifted his focus to the fluoroquinolone inhibitors of bacterial DNA topoisomerases. Studies of fluoroquinolone mechanism and resistance were aimed at combatting the expanding problem of antimicrobial-resistant bacterial infections, in particular tuberculosis. In collaboration with Xilin Zhao, Drlica developed the idea that resistant mutant subpopulations are selectively enriched within a specific range of antimicrobial concentration. This concept revealed a fundamental flaw in our antimicrobial dosing strategies, since with most drug-pathogen combinations the concentrations within patients fall in the mutant-enriching range and thus encourage the emergence of resistance. Drlica's work is currently focused onimproving the lethal activity of antimicrobials to suppress the enrichment of induced and pre-existing mutant subpopulations. Drlica has also served on NIH Study Sections, on the editorial board of several scientific journals, and as a consultant for patent disputes involving gene cloning and fluoroquinolones. His publications include three books (Understanding DNA and Gene Cloning, Double-Edged Sword, Antibiotic Resistance), and with Dr. Fong he has edited two others. Drlica has carried out his work as a member of the faculty of the University of Rochester and the Public Health Research Institute (now a part of Rutgers University) with visiting scientist positions at the Pasteur Institute (Paris), University of California (Berkeley), and the Indian Institute for Science (Bangalore).