Developing target product profiles for Neisseria gonorrhoeae diagnostics in the context of antimicrobial resistance: An expert consensus

Abstract

Background There is a need for a rapid diagnostic point of care test to detect Neisseria gonorrhoeae (NG) infection to prevent incorrect, lack or excess of treatment resulting from current syndromic management in low-resource settings. An assay to identify NG antimicrobial resistance (AMR) is also highly desirable to facilitate antibiotic stewardship. Here we describe the development of two target product profiles (TPPs): one for a test for etiological diagnosis of NG and Chlamydia trachomatis (CT) (TPP1) and one for the detection of NG AMR/susceptibility (TPP2). Methods Draft TPPs were initially developed based on a landscape analysis of existing diagnostics and expert input. TPPs were refined via an online Delphi survey with two rounds of input from 68 respondents. TPP characteristics on which <75% of non-industry respondents agreed were further discussed and revised by an expert working group.

Leapfrogging laboratories: the promise and pitfalls of high-tech solutions for antimicrobial resistance surveillance in low-income settings

“…It would discriminate multiple pathogens associated with a specific syndrome and would be able to read out, or be paired with a second rapid test that identifies, AMR. TPPs along these lines have been issued for gonococcal clinical diagnostics and surveillance 10 and similar profiles would be applicable for febrile illnesses, meningitis and invasive diarrhoea. A decade ago, it would have been challenging or impossible to respond to such a TPP.…”

High-Resolution Melting Analysis to Detect Antimicrobial Resistance Determinants in South African Neisseria gonorrhoeae Clinical Isolates and Specimens

“…Molecular antimicrobial resistance testing is imperative for the control of N. gonorrhoeae , to facilitate antibiotic stewardship, to expedite appropriate treatment of patients, and to conserve the effectiveness of the current treatment regimen [ 21 ]. A recent study projected that continued empiric treatment without antimicrobial susceptibility testing at the POC would result in >5% of N. gonorrhoeae isolates being resistant to both azithromycin and ceftriaxone within 15 years, but the use of a molecular assay could delay the emergence of resistance by 5 years [ 22 , 23 ].…”

“…Currently, the only commercially available genotypic resistance testing assay for N. gonorrhoeae is from SpeeDX (Australia), which determines resistance to ciprofloxacin by detecting the gyrA_S91F mutation. However, due to the high prevalence of resistance to ciprofloxacin in South Africa and other African countries [ 21 ], additional assays to detect genotypic resistance to other drugs are necessary.…”

Visible colorimetric growth indicators of Neisseria gonorrhoeae for low-cost diagnostic applications

“…For N . gonorrhoeae , phenotypic antibiotic susceptibility testing remains standard due largely to the cost of genotypic testing and the vast array of genes involved in resistance [ 4 , 5 ]. Low-cost and point-of-care diagnostics for identification of N .…”

“…The rapidly developing multi-drug resistance of Neisseria gonorrhoeae has been identified as a major public health threat by the World Health Organization [1], the National Institute of Health [2], and the Centers for Disease Control [3]. For N. gonorrhoeae, phenotypic antibiotic susceptibility testing remains standard due largely to the cost of genotypic testing and the vast array of genes involved in resistance [4,5]. Low-cost and point-of-care diagnostics for identification of N. gonorrhoeae infections have increased the number of patients treated compared to symptomatic management alone [6,7], however, increased treatment without careful consideration of specific antibiotics used may drive further antibiotic resistance in this organism [8].…”