To Örebro University

oru.seÖrebro University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Pharmacodynamic evaluation of ceftriaxone single-dose therapy (0.125-1 g) to eradicate ceftriaxone-susceptible and ceftriaxone-resistant Neisseria gonorrhoeae strains in a hollow fibre infection model for gonorrhoea
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Sexually Transmitted Infections, Örebro University, Örebro, Sweden; Institute for Global Health, University College London (UCL), London, UK.ORCID iD: 0000-0003-1710-2081
Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Sexually Transmitted Infections, Örebro University, Örebro, Sweden.ORCID iD: 0000-0002-0688-2521
Örebro University Hospital. Örebro University, School of Medical Sciences. Division of Clinical Chemistry, Department of Laboratory Medicine.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
Show others and affiliations
2024 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 79, no 5, p. 1006-1013Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Antimicrobial resistance in Neisseria gonorrhoeae is threatening the gonorrhoea treatment, and optimizations of the current ceftriaxone-treatment regimens are crucial. We evaluated the pharmacodynamics of ceftriaxone single-dose therapy (0.125-1 g) against ceftriaxone-susceptible and ceftriaxone-resistant gonococcal strains, based on EUCAST ceftriaxone-resistance breakpoint (MIC > 0.125 mg/L), in our hollow fibre infection model (HFIM) for gonorrhoea.

METHODS: Gonococcal strains examined were WHO F (ceftriaxone-susceptible, MIC < 0.002 mg/L), R (ceftriaxone-resistant, MIC = 0.5 mg/L), Z (ceftriaxone-resistant, MIC = 0.5 mg/L) and X (ceftriaxone-resistant, MIC = 2 mg/L). Dose-range HFIM 7 day experiments simulating ceftriaxone 0.125-1 g single-dose intramuscular regimens were conducted.

RESULTS: Ceftriaxone 0.125-1 g single-dose treatments rapidly eradicated WHO F (wild-type ceftriaxone MIC). Ceftriaxone 0.5 and 1 g treatments, based on ceftriaxone human plasma pharmacokinetic parameters, eradicated most ceftriaxone-resistant gonococcal strains (WHO R and Z), but ceftriaxone 0.5 g failed to eradicate WHO X (high-level ceftriaxone resistance). When simulating oropharyngeal gonorrhoea, ceftriaxone 0.5 g failed to eradicate all the ceftriaxone-resistant strains, while ceftriaxone 1 g eradicated WHO R and Z (low-level ceftriaxone resistance) but failed to eradicate WHO X (high-level ceftriaxone resistance). No ceftriaxone-resistant mutants were selected using any ceftriaxone treatments.

CONCLUSIONS: Ceftriaxone 1 g single-dose intramuscularly cure most of the anogenital and oropharyngeal gonorrhoea cases caused by the currently internationally spreading ceftriaxone-resistant gonococcal strains, which should be further confirmed clinically. A ceftriaxone 1 g dose (±azithromycin 2 g) should be recommended for first-line empiric gonorrhoea treatment. This will buy countries some time until novel antimicrobials are licensed. Using ceftriaxone 1 g gonorrhoea treatment, the EUCAST ceftriaxone-resistance breakpoint is too low.

Place, publisher, year, edition, pages
Oxford University Press, 2024. Vol. 79, no 5, p. 1006-1013
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:oru:diva-112439DOI: 10.1093/jac/dkae063ISI: 001186493700001PubMedID: 38497988Scopus ID: 2-s2.0-85192114004OAI: oai:DiVA.org:oru-112439DiVA, id: diva2:1845852
Funder
Region Örebro CountyAvailable from: 2024-03-20 Created: 2024-03-20 Last updated: 2024-06-10Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records

Unemo, MagnusGolparian, DanielOxelbark, JoakimJacobsson, Susanne

Search in DiVA

By author/editor
Unemo, MagnusGolparian, DanielOxelbark, JoakimJacobsson, Susanne
By organisation
School of Medical SciencesÖrebro University Hospital
In the same journal
Journal of Antimicrobial Chemotherapy
Infectious Medicine

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 306 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf