Emergence and #spread of #ciprofloxacin-resistant Neisseria #gonorrhoeae in #NSW, #Australia: lessons from history (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Emergence and spread of ciprofloxacin-resistant Neisseria gonorrhoeae in New South Wales, Australia: lessons from history

Jane K Hanrahan, Tiffany R Hogan, Cameron Buckley, Ella Trembizki, Hazel Mitchell, Colleen L Lau, David M Whiley, Monica M Lahra

Journal of Antimicrobial Chemotherapy, dkz182, https://doi.org/10.1093/jac/dkz182

Published: 06 June 2019

 

Abstract

Objectives

Our aim was to investigate the emergence and spread of ciprofloxacin resistance in clinical Neisseria gonorrhoeae isolates in New South Wales, Australia, from the first reported case in 1991 until ciprofloxacin resistance was sustained at or above the WHO threshold for treatment change of 5% (1999), to inform future strategies for controlling gonococcal antimicrobial resistance.

Methods

The index isolate and all subsequent clinical isolates of ciprofloxacin-resistant N. gonorrhoeae in New South Wales from 1991 to 1999 were genotyped using a previously described method on the Agena MassARRAY iPLEX platform. Region of acquisition data, where available, were used to determine whether cases were travel associated.

Results

In New South Wales, of the 325 ciprofloxacin-resistant N. gonorrhoeae isolates reported from 1991 to 1999, 98% (320/325) were able to be recovered and 100% (320/320) were genotyped. There were 66 different genotypes, comprising 1–99 isolates each. Notably no single clone was found to account for ciprofloxacin resistance being sustained in the population, with considerable variability in genotype prevalence observed throughout the study period. A total of 65% (209/320) of genotyped isolates had information regarding the likely place of acquisition; of these, 44% (93/209) were associated with overseas travel or sexual contact with an overseas visitor. The first ciprofloxacin-resistant N. gonorrhoeae in New South Wales was associated with travel to Thailand. Index cases of each resistant genotype were significantly more likely to have been acquired overseas (51.5%), predominantly in Asia (45%, 30/66).

Conclusions

The continued importation of multiple genotypes, rather than the expansion of a single genotype, led to ciprofloxacin-resistant N. gonorrhoeae being established in New South Wales.

Topic: ciprofloxacin – gonococcal infection – asia – australia – drug resistance, microbial – genotype – neisseria gonorrhoeae – new south wales – thailand – travel – world health organization

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Ciprofloxacin; Neisseria gonorrhoeae; New South Wales; Australia.

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#Gentamicin compared with #ceftriaxone for the #treatment of #gonorrhoea (G-ToG): a randomised non-inferiority trial (Lancet, abstract)

[Source: The Lancet, full page: (LINK). Abstract, edited.]

Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial

Prof Jonathan D C Ross, MD, Clare Brittain, BMedSc, Michelle Cole, DBMS, Claire Dewsnap, MD, Jan Harding, PhD, Trish Hepburn, BSc, Louise Jackson, PhD, Matthew Keogh, Tessa Lawrence, PhD, Prof Alan A Montgomery, PhD, Prof Tracy E Roberts, PhD, Kirsty Sprange, MSc, Wei Tan, MSc, Sukhwinder Thandi, PhD, John White, FRCP, Janet Wilson, FRCP, Prof Lelia Duley, MD, on behalf of theG-ToG trial team

Published: May 02, 2019 / DOI: https://doi.org/10.1016/S0140-6736(18)32817-4

 

Summary

Background

Gonorrhoea is a common sexually transmitted infection for which ceftriaxone is the current first-line treatment, but antimicrobial resistance is emerging. The objective of this study was to assess the effectiveness of gentamicin as an alternative to ceftriaxone (both combined with azithromycin) for treatment of gonorrhoea.

Methods

G-ToG was a multicentre, parallel-group, pragmatic, randomised, non-inferiority trial comparing treatment with gentamicin to treatment with ceftriaxone for patients with gonorrhoea. The patients, treating physician, and assessing physician were masked to treatment but the treating nurse was not. The trial took place at 14 sexual health clinics in England. Adults aged 16–70 years were eligible for participation if they had a diagnosis of uncomplicated genital, pharyngeal, or rectal gonorrhoea. Participants were randomly assigned to receive a single intramuscular dose of either gentamicin 240 mg (gentamicin group) or ceftriaxone 500 mg (ceftriaxone group). All participants also received a single 1 g dose of oral azithromycin. Randomisation (1:1) was stratified by clinic and performed using a secure web-based system. The primary outcome was clearance of Neisseria gonorrhoeae at all initially infected sites, defined as a negative nucleic acid amplification test 2 weeks post treatment. Primary outcome analyses included only participants who had follow-up data, irrespective of the baseline visit N gonorrhoeae test result. The margin used to establish non-inferiority was a lower confidence limit of 5% for the risk difference. This trial is registered with ISRCTN, number ISRCTN51783227.

Findings

Of 1762 patients assessed, we enrolled 720 participants between Oct 7, 2014, and Nov 14, 2016, and randomly assigned 358 to gentamicin and 362 to ceftriaxone. Primary outcome data were available for 306 (85%) of 362 participants allocated to ceftriaxone and 292 (82%) of 358 participants allocated to gentamicin. At 2 weeks after treatment, infection had cleared for 299 (98%) of 306 participants in the ceftriaxone group compared with 267 (91%) of 292 participants in the gentamicin group (adjusted risk difference −6·4%, 95% CI −10·4% to −2·4%). Of the 328 participants who had a genital infection, 151 (98%) of 154 in the ceftriaxone group and 163 (94%) of 174 in the gentamicin group had clearance at follow-up (adjusted risk difference −4·4%, −8·7 to 0). For participants with a pharyngeal infection, a greater proportion receiving ceftriaxone had clearance at follow-up (108 [96%] in the ceftriaxone group compared with 82 [80%] in the gentamicin group; adjusted risk difference −15·3%, −24·0 to −6·5). Similarly, a greater proportion of participants with rectal infection in the ceftriaxone group had clearance (134 [98%] in the ceftriaxone group compared with 107 [90%] in the gentamicin group; adjusted risk difference −7·8%, −13·6 to −2·0). Thus, we did not find that a single dose of gentamicin 240 mg was non-inferior to a single dose of ceftriaxone 500 mg for the treatment of gonorrhoea, when both drugs were combined with a 1 g dose of oral azithromycin. The side-effect profiles were similar between groups, although severity of pain at the injection site was higher for gentamicin (mean visual analogue pain score 36 of 100 in the gentamicin group vs 21 of 100 in the ceftriaxone group).

Interpretation

Gentamicin is not appropriate as first-line treatment for gonorrhoea but remains potentially useful for patients with isolated genital infection, or for patients who are allergic or intolerant to ceftriaxone, or harbour a ceftriaxone-resistant isolate. Further research is required to identify and test new alternatives to ceftriaxone for the treatment of gonorrhoea.

Funding

UK National Institute for Health Research.

Keywords: Antibiotics; Drugs Resistance; Neisseria gonorrhoeae; Ceftriaxone; Azithromycin; Gentamicin.

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#Clonal expansion and spread of the #ceftriaxone-resistant #Neisseria gonorrhoeae strain FC428, identified in #Japan in 2015, and closely related isolates (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Clonal expansion and spread of the ceftriaxone-resistant Neisseria gonorrhoeae strain FC428, identified in Japan in 2015, and closely related isolates

Kenichi Lee, Shu-Ichi Nakayama, Kayo Osawa, Hiroyuki Yoshida, Soichi Arakawa, Kei-Ichi Furubayashi, Hiroshi Kameoka, Ken Shimuta, Takuya Kawahata, Magnus Unemo, Makoto Ohnishi

Journal of Antimicrobial Chemotherapy, dkz129, https://doi.org/10.1093/jac/dkz129

Published: 19 April 2019

 

Abstract

Objectives

Ceftriaxone resistance in Neisseria gonorrhoeae is a major public health concern globally because a high-dose (1 g) injection of ceftriaxone is the only remaining option for empirical monotherapy of gonorrhoea. The ceftriaxone-resistant gonococcal strain FC428, cultured in Osaka in 2015, is suspected to have spread nationally and internationally. We describe the complete finished genomes of FC428 and two closely related isolates from Osaka in 2015, and examine the genomic epidemiology of these isolates plus three ceftriaxone-resistant gonococcal isolates from Osaka and Hyogo in 2016–17 and four ceftriaxone-resistant gonococcal isolates cultured in 2017 in Australia, Canada and Denmark.

Methods

During 2015–17, we identified six ceftriaxone-resistant gonococcal isolates through our surveillance systems in Kyoto, Osaka and Hyogo. Antimicrobial susceptibility testing (six antimicrobials) was performed using Etest. Complete whole-genome sequences of the first three isolates (FC428, FC460 and FC498) from 2015 were obtained using PacBio RS II and Illumina MiSeq sequencing. The three complete genome sequences and draft genome sequences of the three additional Japanese (sequenced with Illumina MiSeq) and four international ceftriaxone-resistant isolates were compared.

Results

Detailed genomic analysis suggested that the Japanese isolates (FC428, FC460, FC498, KU16054, KM383 and KU17039) and the four international MLST ST1903 isolates from Australia, Canada and Denmark formed four linked subclades.

Conclusions

Using detailed genomic analysis, we describe the clonal expansion of the ceftriaxone-resistant N. gonorrhoeae strain FC428, initially identified in 2015 in Japan, and closely related isolates. FC428 and its close relatives show some genomic diversity, suggesting multiple genetic subclades are already spreading internationally.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Ceftriaxone; Neisseria gonorrhoeae; Japan.

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First Case of #Ceftriaxone- #Resistant #MDR #Neisseria gonorrhoeae in #Singapore (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

First Case of Ceftriaxone-Resistant Multidrug-Resistant Neisseria gonorrhoeae in Singapore

Karrie Kwan Ki Ko, Martin TW Chio, Sui Sin Goh, Ai Ling Tan, Tse Hsien Koh, Nurdyana Binte Abdul Rahman

DOI: 10.1128/AAC.02624-18

 

ABSTRACT

Amid the global crisis of increasing gonococcal antimicrobial resistance, we report the first case of ceftriaxone-resistant multidrug-resistant Neisseria gonorrhoeae in Singapore.…

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Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs resistance; Neisseria gonorrhoeae; Singapore.

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Emergence of #Neisseria gonorrhoeae Strains Harboring a Novel #Combination of #Azithromycin-#attenuator Mutations (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Emergence of Neisseria gonorrhoeae Strains Harboring a Novel Combination of Azithromycin-attenuator Mutations.

Cau D. Pham, Samera Sharpe, Karen Schlanger, Sancta St Cyr, Justin Holderman, Richard Steece, Olusegun O. Soge, Godfred Masinde, Janet Arno, Matthew Schmerer, Ellen N. Kersh,the SURRG Working Group

DOI: 10.1128/AAC.02313-18

 

ABSTRACT

The nimbleness of N. gonorrhoeae to evade the effect of antibiotics has perpetuated the fight against antibiotic-resistant gonorrhea for more than 80 years. The ability to develop resistance to antibiotics is attributable to its indiscriminate nature in accepting and integrating exogenous DNA into its genome. Here, we provide data demonstrating a novel combination of the 23S rRNA A2059G mutation with a mosaic-mtr locus haplotype in fourteen N. gonorrhoeae isolates with high-level azithromycin MICs (≥ 256 μg/ml), a combination that may confer more fitness than previously identified isolates with high-level azithromycin resistance. To our knowledge, this is the first description of N. gonorrhoeae strains harboring this novel combination of resistance determinants. These strains were isolated at two independent jurisdictions participating in the Gonococcal Isolate Surveillance Project (GISP) and in the Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) project. The data suggest that N. gonorrhoeae’s genome continues to shuffle its genetic material. These findings further illuminate the genomic plasticity of N. gonorrhoeae, which allows this pathogen to develop mutations to escape the inhibitory effects of antibiotics.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Neisseria gonorrhoeae; Azithromycin.

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Evaluation of #apramycin against #spectinomycin-resistant and -susceptible strains of #Neisseria gonorrhoeae (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Evaluation of apramycin against spectinomycin-resistant and -susceptible strains of Neisseria gonorrhoeae

Stefan Riedel, Divya Vijayakumar, Gretchen Berg, Anthony D Kang, Kenneth P Smith, James E Kirby

Journal of Antimicrobial Chemotherapy, dkz012, https://doi.org/10.1093/jac/dkz012

Published: 27 January 2019

 

Abstract

Background

The emergence of Neisseria gonorrhoeae resistant to all currently available antimicrobial therapies poses a dire public health threat. New antimicrobial agents with activity against N. gonorrhoeae are urgently needed. Apramycin is an aminocyclitol aminoglycoside with broad-spectrum in vitro activity against MDR Gram-negative pathogens and Staphylococcus aureus. However, its activity against N. gonorrhoeae has not been described.

Objectives

The activity spectrum of apramycin against a collection of MDR N. gonorrhoeaewas assessed. Isolates tested included those susceptible and resistant to the structurally distinct aminocyclitol, spectinomycin.

Results

The modal MICs for apramycin and spectinomycin were 16 mg/L and 32 mg/L, respectively. The epidemiological cut-off (ECOFF) for apramycin was 64 mg/L. No strains among 77 tested had an MIC above this ECOFF, suggesting very low levels of acquired apramycin resistance. In time–kill analysis, apramycin demonstrated rapid bactericidal activity comparable to that of spectinomycin.

Conclusions

Apramycin has broad-spectrum, rapidly bactericidal activity against N. gonorrhoeae. Future pharmacokinetic and pharmacodynamic studies will be needed to determine whether apramycin and/or apramycin derivatives hold promise as new therapeutics for N. gonorrhoeae infection.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Neisseria gonorrhoeae; Spectinomycin; Apramycin; Aminoglycosides.

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#Photoinactivation of #Neisseria gonorrhoeae: A paradigm changing approach for combating #antibiotic-resistant gonococcal #infection (J Infect Dis., abstract)

[Source: The Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Photo-inactivation of Neisseria gonorrhoeae: A paradigm changing approach for combating antibiotic-resistant gonococcal infection

Ying Wang, Raquel Ferrer-Espada, Yan Baglo, Xueping S Goh, Kathryn D Held, Yonatan H Grad, Ying Gu, Jeffrey A Gelfand, Tianhong Dai

The Journal of Infectious Diseases, jiz018, https://doi.org/10.1093/infdis/jiz018

Published: 09 January 2019

 

Abstract

Antimicrobial resistance in Neisseria gonorrhoeae is a major issue of public health, and there is a critical need for the development of new anti-gonococcal strategies. In this study, we investigated the effectiveness of antimicrobial blue light (aBL; 405 nm wavelength), an innovative non-pharmacological approach, for the inactivation of N. gonorrhoeae. Our findings indicated that aBL preferentially inactivated N. gonorrhoeae, including antibiotic-resistant strains, over human vaginal epithelial cells in vitro. Furthermore, no genotoxicity of aBL to the vaginal epithelial cells was observed at the radiant exposure for inactivating N. gonorrhoeae. aBL also effectively inactivated N. gonorrhoeae that had attached to and invaded into the vaginal epithelial cells in their co-cultures.No gonococcal resistance to aBL developed after 15 successive cycles of sub-therapeutic aBL inactivation. Endogenous aBL-activatable photosensitizing porphyrins in N. gonorrhoeae were identified and quantified using ultra-performance liquid chromatography, with coproporphyrin being the most abundant species in all the N. gonorrhoeae strains studied. Singlet oxygen was involved in aBL inactivation of N. gonorrhoeae. Taken together, aBL represents a potent potential treatment for antibiotic-resistant gonococcal infection.

Topic: abetalipoproteinemia – antibiotic resistance, bacterial – gonococcal infection – liquid chromatography – coculture techniques – coproporphyrins – drug resistance, microbial – neisseria gonorrhoeae – porphyrins – singlet oxygen – pharmacology – public health medicine – vagina – antimicrobials – epithelial cells – blue light

Issue Section: Major Article

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Neisseria gonorrhoeae; Blue light.

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