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

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Unemo, Magnus,1970-Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,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 (author)

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

Article/chapterEnglish2024

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Oxford University Press,2024
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LIBRIS-ID:oai:DiVA.org:oru-112439
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-112439URI
https://doi.org/10.1093/jac/dkae063DOI

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Summary in:English

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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.

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Golparian, Daniel,1984-Örebro universitet,Institutionen för medicinska vetenskaper,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(Swepub:oru)degn (author)
Oxelbark, Joakim,1970-Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Division of Clinical Chemistry, Department of Laboratory Medicine(Swepub:oru)jok (author)
Kong, Fabian Y SCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia (author)
Brown, DavidInstitute for Therapeutic Innovation, College of Medicine, University of Florida, Gainesville, FL, USA (author)
Louie, ArnoldInstitute for Therapeutic Innovation, College of Medicine, University of Florida, Gainesville, FL, USA (author)
Drusano, GeorgeInstitute for Therapeutic Innovation, College of Medicine, University of Florida, Gainesville, FL, USA (author)
Jacobsson, Susanne,1974-Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Department of Laboratory Medicine, Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Sexually Transmitted Infections(Swepub:oru)sajn (author)
Örebro universitetInstitutionen för medicinska vetenskaper (creator_code:org_t)

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In:Journal of Antimicrobial Chemotherapy: Oxford University Press79:5, s. 1006-10130305-74531460-2091

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