Is gentamicin a viable therapeutic option for treating resistant Neisseria gonorrhoeae in New South Wales?

Abstract

The key issues with Neisseria gonorrhoeae infections, in Australia and elsewhere, are coincident increases in disease rates and in antimicrobial resistance (AMR), although these factors have not been shown to be correlated. Despite advances in diagnosis, control of this disease remains elusive, and incidence in Australia continues to increase. Of the Australian jurisdictions, New South Wales (NSW) has the highest N. gonorrhoeae notifications, and over the five-year period 2015-2019, notifications in NSW have increased above the national average (by 116% versus 85%, respectively). Gonococcal disease control is reliant on effective antibiotic regimens. However, escalating AMR in N. gonorrhoeae is a global health priority, as the collateral injury of untreated infections has substantive impacts on sexual and newborn health. Currently, our first-line therapy for gonorrhoea is also our last line, with no ideal alternative identified. Despite some limitations, gentamicin is licensed and readily available in Australia, and is proposed for treatment of resistant N. gonorrhoeae in national guidelines; however, supportive published microbiological data are lacking. Analysis of gonococcal resistance patterns within Australia for the period 1991-2019, including 35,000 clinical isolates from NSW, illustrates the establishment and spread of population-level resistance to all contemporaneous therapies. An analysis of gentamicin susceptibility on 2,768 N. gonorrhoeae clinical isolates from NSW, for the period 2015-2020, demonstrates that the median minimum inhibitory concentration (MIC) for gentamicin in NSW has remained low, at 4.0 mg/L, and resistance was not detected in any isolate. There has been no demonstration of MIC drift over time (p = 0.91, Kruskal-Wallis test), nor differences in MIC distributions according to patients' sex or site of specimen collection. This is the first large-scale evaluation of gentamicin susceptibility in N. gonorrhoeae in Australia. No gentamicin resistance was detected in clinical isolates, 2015-2020, hence this is likely to be an available treatment option for resistant gonococcal infections in NSW.

Keywords: Neisseria gonorrhoeae; antimicrobial resistance; gentamicin; gonococcal; surveillance; treatment.