Research Article: Multidrug-resistant gonorrhea: A research and development roadmap to discover new medicines

Date Published: July 26, 2017

Publisher: Public Library of Science

Author(s): Emilie Alirol, Teodora E. Wi, Manju Bala, Maria Luiza Bazzo, Xiang-Sheng Chen, Carolyn Deal, Jo-Anne R. Dillon, Ranmini Kularatne, Jutta Heim, Rob Hooft van Huijsduijnen, Edward W. Hook, Monica M. Lahra, David A. Lewis, Francis Ndowa, William M. Shafer, Liz Tayler, Kimberly Workowski, Magnus Unemo, Manica Balasegaram

Abstract: Emilie Alirol and colleagues discuss the development of new treatments for gonorrhea.

Partial Text: Gonorrhea is among the most common sexually transmitted infections (STIs), with an estimated 78 million new cases in 2012 [1]. Countries with good surveillance have reported increases in cases of gonorrhea, such as an 11% rise between 2014 and 2015 in the United Kingdom [2], a doubling of cases among MSM (men who have sex with men) in France between 2013 and 2015 [3], a 5% rise between 2013 and 2015 in the United States [4], and an increase of 29%–146% in almost all Australian states between 2010 and 2014 [5], all reflecting longer-term trends. Decreasing condom use [6], increased urbanization and travel, poor infection detection rates, and inadequate or failed treatment [7] all contribute to this increase.

As a disease that is not usually deadly but affects millions of people, gonorrhea control initiatives lack sufficient coordination and investment. With increasingly limited treatment options in the wider context of AMR, there is now growing concern that the threat of untreatable gonorrhea will become a reality. In February 2017, WHO listed N. gonorrhoeae among “High Priority” pathogens for research and development (R&D) of new antibiotics [60]. While hospital-acquired pathogens may have been highest on the list because of the high rates of mortality they cause, N. gonorrhoeae was notably included because infections are extremely widespread, cause substantial morbidity with a significant health cost for countries, can affect pregnant women and their babies, and develop AMR at a particularly rapid pace. Gonorrhea was also listed by the US Centers for Disease Control and Prevention (CDC) in the top “Urgent Threat” category of 18 drug-resistant threats to the US [61] and is included in similar AMR priority lists in the UK and Canada.

At the 68th World Health Assembly in 2015, WHO adopted the Global Action Plan on Antimicrobial Resistance. One of the Plan’s initiatives was the launch of the Global Antibiotic Research and Development Partnership (GARDP; in May 2016 [73]. GARDP is hosted and governed by the Drugs for Neglected Diseases initiative (DNDi) and has set up several programs aimed at developing new treatments in the short- to medium-term for STIs, neonatal sepsis, and an antimicrobial memory-recovery initiative. The latter aims to retrieve drugs and drug candidates (and associated expertise) whose use or development were halted in the past for reasons that no longer apply (e.g., Pharma portfolio considerations).

The number of gonococcal infections is rapidly rising worldwide. Most worrisome, N. gonorrhoeae is an important member of the bacterial community that spreads AMR. Just 3 new clinical entities are in various stages of clinical development for treatment of gonorrhea today, in a therapeutic area that lacks a strong commercial interest. GARDP, a joint initiative founded by WHO and DNDi, has begun to document ideal and acceptable profiles of antimicrobials for gonorrhea treatment. Four R&D routes have been outlined that require donor support: introduction of a new molecule for gonorrhea, identification of ideal combination partners among existing antibiotics, formulation of new fixed drug combinations, and establishment of a stewardship framework for the distribution and use of the new treatments. GARDP intends to work with its partners and other stakeholders to complete this roadmap and bring at least 1 new treatment into clinical practice by 2023.



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