1. Clin Microbiol Infect. 2020 Dec;26(12):1630-1635. doi: 
10.1016/j.cmi.2020.08.006. Epub 2020 Aug 13.

Pharmacokinetic/pharmacodynamic considerations for new and current therapeutic 
drugs for uncomplicated gonorrhoea-challenges and opportunities.

Theuretzbacher U(1), Barbee L(2), Connolly K(3), Drusano G(4), Fernandes P(5), 
Hook E(6), Jerse A(3), O'Donnell J(7), Unemo M(8), Van Bambeke F(9), VanScoy 
B(10), Warn P(11), Werth BJ(12), Franceschi F(13), Alirol E(13).

Author information:
(1)Centre for Anti-Infective Agents, Vienna, Austria. Electronic address: 
utheuretzbacher@cefaia.com.
(2)University of Washington, Division of Allergy and Infectious Diseases, 
Department of Medicine, Seattle, WA, USA.
(3)Uniformed Services University, Bethesda, MD, USA.
(4)Institute for Therapeutic Innovation, University of Florida, Lake Nona, FL, 
USA.
(5)Chair, Scientific Advisory Committee, GARDP, Geneva, Switzerland.
(6)University of Alabama at Birmingham, Birmingham, AL, USA.
(7)Entasis Therapeutics, Waltham, MA, USA.
(8)WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted 
Infections, Örebro University, Örebro, Sweden.
(9)Université Catholique de Louvain, Brussels, Belgium.
(10)Institute for Clinical Pharmacodynamics, Latham, New York, USA.
(11)Magic Bullet Consulting, London, UK.
(12)University of Washington, School of Pharmacy, Seattle, WA, USA.
(13)Global Antibiotic R&D Partnership (GARDP), Geneva, Switzerland.

BACKGROUND: Increasing multidrug resistance rates in Neisseria gonorrhoeae have 
raised concerns and an urgent call for new antibiotics for treatment of 
gonorrhoea. Several decades of subdued drug development in this field and the 
recent failures of two new antibiotics to show non-inferiority compared with the 
current first-line antibiotics ceftriaxone plus azithromycin highlight the need 
for improved preclinical tools to predict clinical outcome of new drugs in the 
development process.
OBJECTIVES: To summarize current pharmacokinetic/pharmacodynamic (PK/PD) 
knowledge and dose-finding strategies for antibiotics against gonorrhoea.
SOURCES: Literature review of published papers and discussions by global experts 
at a special workshop on this topic.
CONTENT: We review current knowledge of gonococcal specific PK/PD principles and 
provide an update on new in vitro and in vivo models to correlate drug exposure 
with clinical outcome, and identify challenges and gaps in gonococcal 
therapeutic research.
IMPLICATIONS: Identifying the ideal antimicrobial agent and dose for treating 
uncomplicated urogenital and pharyngeal gonococcal disease requires appropriate 
validated non-clinical PK/PD models. Recent advances in adapting in vitro and 
in vivo models for use in gonorrhoea are an important step for enabling the 
development of new drugs with reduced risk of failure in Phase 3 clinical 
development and diminish the risk of emergence of resistance.

Copyright © 2020. Published by Elsevier Ltd.

DOI: 10.1016/j.cmi.2020.08.006
PMID: 32798687