Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study

Sánchez-Busó, Leonor; Cole, Michelle; Spiteri, Gianfranco; Day, Michaela; Jacobsson, Susanne; Golparian, Daniel; Sajedi, Noshin; Yeats, Corin; Abudahab, Khalil; Underwood, Anthony; Bluemel, Benjamin; Aanensen, David M.; Pleininger, Sonja; Indra, Alexander; Baetselier, Irith De; Berghe, Wim Vanden; Hunjak, Blaženka; Blažić, Tatjana Nemeth; Maikanti-Charalambous, Panayiota; Pieridou, Despo; Zákoucká, Hana; Žemličková, Helena; Hoffmann, Steen; Cowan, Susan; Schwartz, Lasse Jessen; Peetso, Rita; Epštein, Jevgenia; Viktorova, Jelena; Ndeikoundam, Ndeindo; Berçot, Béatrice; Bebear, Cécile; Lot, Florence; Buder, Susanne; Jansen, Klaus; Miriagou, Vivì; Rigakos, Georgios; Raftopoulos, Vasilios; Balla, Eszter; Dudás, Mária; Ásmundsdóttir, Lena Rós; Sigmundsdóttir, Guðrún; Hauksdóttir, Guðrún Svanborg; Guðnason, Þórólfur; Colgan, Aoife; Crowley, Brendan; Saab, Sinéad; Stefanelli, Paola; Carannante, Anna; Parodi, Patrizia; Pakarna, Gatis; Nikiforova, Raina; Bormane, Antra; Dimiņa, Elīna; Perrin, Monique; Abdelrahman, Tamer; Mossong, Joël; Schmit, Jean-Claude; Mühlschlegel, Friedrich; Barbara, Christopher; Mifsud, Francesca; Dam, Alje P. van; Benthem, Birgit van; Visser, Maartje; Linde, Ineke; Kløvstad, Hilde; Caugant, Dominique; Młynarczyk-Bonikowska, Beata; Azevedo, Jacinta; Borrego, Maria-José; Nascimento, Marina Lurdes Ramos; Pavlik, Peter; Klavs, Irena; Murnik, Andreja; Jeverica, Samo; Kustec, Tanja; Moreno, Julio Vázquez; Díaz, Asunción; Abad, Raquel; Veličko, Inga; Unemo, Magnus; Fifer, Helen; Shepherd, Jill; Patterson, Lynsey

doi:10.1016/s2666-5247(22)00044-1

Cited by 51 publications

(91 citation statements)

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“…Resistance or decreased susceptibility to ceftriaxone and azithromycin resistance in N. gonorrhoeae has been reported worldwide [ 22 ]. In recent years in Europe, the susceptibility to ceftriaxone has increased but, worryingly, the resistance to azithromycin rapidly increased [ 19 , 23 ]. Furthermore, sporadic ceftriaxone-resistant strains have been identified in several European countries [ 1 , 5 , 7 , 15 , 18 , 19 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…In recent years in Europe, the susceptibility to ceftriaxone has increased but, worryingly, the resistance to azithromycin rapidly increased [ 19 , 23 ]. Furthermore, sporadic ceftriaxone-resistant strains have been identified in several European countries [ 1 , 5 , 7 , 15 , 18 , 19 , 22 , 23 ]. However, the XDR strain described in the present paper is the second global gonococcal strain with ceftriaxone resistance combined with high-level azithromycin resistance, with relatively close relationship with WHO Q [ 7 , 8 ], although not the same subvariant ( Figure ).…”

Section: Discussionmentioning

confidence: 99%

“…If such strains manage to establish a sustained transmission, many gonorrhoea cases might become untreatable. Promisingly, the XDR AT159 strain had wild-type MICs of the novel gonorrhoea antimicrobials lefamulin and zoliflodacin, which is in a phase 3 randomised clinical trial [ 10 , 12 , 19 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Genome assemblies of closely related Asian isolates (n = 70) [ 12 ] to AT159 (orange star) were uploaded and analysed on the Pathogenwatch platform [ 9 , 19 ] including a phylogenetic inference. Briefly, Pathogenwatch [ 9 ] provides a cgMLST defined by the 2016 Neisseria gonorrhoeae reference strains [ 20 ] and each assembly is linked to the closest reference by comparing the substitution score profiles to the reference core profiles excluding indels and non-ACTG characters.…”

Section: Clinical Case Description and Microbiologymentioning

confidence: 99%

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Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022

et al. 2022

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We describe a gonorrhoea case with ceftriaxone plus high-level azithromycin resistance. In April 2022, an Austrian heterosexual male was diagnosed with gonorrhoea after sexual intercourse with a female sex worker in Cambodia. Recommended treatment with ceftriaxone (1 g) plus azithromycin (1.5 g) possibly failed. Worryingly, this is the second strain in an Asian Neisseria gonorrhoeae genomic sublineage including high-level azithromycin-resistant strains that developed ceftriaxone resistance by acquisition of mosaic penA-60.001. Enhanced resistance surveillance and actions are imperative to prevent spread.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Clinical Case Description and Microbiologymentioning

confidence: 99%

See 2 more Smart Citations

Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022

et al. 2022

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“…There is now good reason to believe that the increased use of AZM in combination therapy with CRO to treat gonorrhoea from 2012 to 2020 selected for strains with a mosaic mtr locus due to recombination events with commensal Neisseria sp. in the oral cavity [67,69,70]. Thus, when considering the introduction of new antibiotics in future clinical regimens it will be prudent to determine if they are subject to efflux by MtrCDE as regulatory mutations could influence their continued efficacy.…”

Section: Contributions and Evolution Of Regulatory Mutations Impactin...mentioning

confidence: 99%

Transcriptional regulation of the mtrCDE efflux pump operon: importance for Neisseria gonorrhoeae antimicrobial resistance

2022

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This review focuses on the mechanisms of transcriptional control of an important multidrug efflux pump system (MtrCDE) possessed by Neisseria gonorrhoeae , the aetiological agent of the sexually transmitted infection termed gonorrhoea. The mtrCDE operon that encodes this tripartite protein efflux pump is subject to both cis- and trans-acting transcriptional factors that negatively or positively influence expression. Critically, levels of MtrCDE can influence levels of gonococcal susceptibility to classical antibiotics, host-derived antimicrobials and various biocides. The regulatory systems that control mtrCDE can have profound influences on the capacity of gonococci to resist current and past antibiotic therapy regimens as well as virulence. The emergence, mechanisms of action and clinical significance of the transcriptional regulatory systems that impact mtrCDE expression in gonococci are reviewed here with the aim of linking bacterial antimicrobial resistance with multidrug efflux capability.

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Urethritis – Erregerspektrum, Diagnostik und Therapie

Buder

2023

Dermatologie

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Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study

Cited by 51 publications

References 30 publications

Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022

Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022

Transcriptional regulation of the mtrCDE efflux pump operon: importance for Neisseria gonorrhoeae antimicrobial resistance

Urethritis – Erregerspektrum, Diagnostik und Therapie

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