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.

[1]  Xiangsheng Chen,et al.  Surveillance and molecular epidemiology of Neisseria gonorrhoeae isolates in Shenzhen, China, from 2010 to 2017. , 2020, Journal of global antimicrobial resistance.

[2]  D. Whiley,et al.  Are sex norms the norm in gonococcal surveillance? , 2020, The Lancet. Microbe.

[3]  Monica Lahra,et al.  Australian Gonococcal Surveillance Programme Annual Report, 2019. , 2020, Communicable diseases intelligence.

[4]  Monica Lahra,et al.  Lessons learnt from ceftriaxone-resistant gonorrhoea in the UK and Australia. , 2020, The Lancet. Infectious diseases.

[5]  M. Golden,et al.  Gentamicin Alone Inadequate to Eradicate Neisseria Gonorrhoeae from the Pharynx. , 2019, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  Monica Lahra,et al.  Emergence and spread of ciprofloxacin-resistant Neisseria gonorrhoeae in New South Wales, Australia: lessons from history. , 2019, The Journal of antimicrobial chemotherapy.

[7]  D. Lewis New treatment options for Neisseria gonorrhoeae in the era of emerging antimicrobial resistance. , 2019, Sexual health.

[8]  Louise J Jackson,et al.  Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial , 2019, The Lancet.

[9]  Monica Lahra,et al.  Treatment for pharyngeal gonorrhoea under threat. , 2018, The Lancet. Infectious diseases.

[10]  W. Demczuk,et al.  Cooperative Recognition of Internationally Disseminated Ceftriaxone-Resistant Neisseria gonorrhoeae Strain , 2018, Emerging infectious diseases.

[11]  M. Unemo,et al.  Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action , 2017, PLoS medicine.

[12]  Richard Gray,et al.  HIV, viral hepatitis and sexually transmissible infections in Australia , 2016 .

[13]  K. Chapin,et al.  Extragenital Infections Caused by Chlamydia trachomatis and Neisseria gonorrhoeae: A Review of the Literature , 2016, Infectious diseases in obstetrics and gynecology.

[14]  S. Manzano,et al.  A New Multidrug-Resistant Strain of Neisseria gonorrhoeae in Australia. , 2015, The New England journal of medicine.

[15]  F. Martinson,et al.  Neisseria gonorrhoeae Antimicrobial Susceptibility in Lilongwe, Malawi, 2007 , 2010, Sexually transmitted diseases.

[16]  F. Zafar,et al.  Oropharyngeal gonorrhoea: rate of co-infection with sexually transmitted infection, antibiotic susceptibility and treatment outcome , 2010, International journal of STD & AIDS.

[17]  J. Tapsall,et al.  Analysis of trends in antimicrobial resistance in Neisseria gonorrhoeae isolated in Australia, 1997 2006. , 2007, The Journal of antimicrobial chemotherapy.

[18]  E. A. Phillips,et al.  Quinolone‐Resistant Neisseria gonorrhoeae Isolated in Sydney, Australia, 1991 to 1995 , 1996, Sexually transmitted diseases.

[19]  J. Billington LESSONS from history. , 1952, Lancet.

[20]  AustrAliAn GonococcAl surveillAnce ProGrAmme AnnuAl rePort , 2022 .