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.
J Antimicrob Chemother
; 79(5): 1006-1013, 2024 05 02.
Article
em En
| MEDLINE
| ID: mdl-38497988
ABSTRACT
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 (MICâ>â0.125 mg/L), in our hollow fibre infection model (HFIM) for gonorrhoea.METHODS:
Gonococcal strains examined were WHO F (ceftriaxone-susceptible, MICâ<â0.002 mg/L), R (ceftriaxone-resistant, MICâ=â0.5 mg/L), Z (ceftriaxone-resistant, MICâ=â0.5 mg/L) and X (ceftriaxone-resistant, MICâ=â2 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ceftriaxona
/
Gonorreia
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Testes de Sensibilidade Microbiana
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Antibacterianos
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Neisseria gonorrhoeae
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article