Assessing novel partner antimicrobials to protect ceftriaxone against gonococcal resistance: An in vitro evaluation
Saïd Abdellati1,2, Zina Gestels1, Yuliia Baranchyk1
1STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Background:
The emergence of ceftriaxone-resistant Neisseria gonorrhoeae poses a significant threat to existing treatment regimens. Our study aimed to assess the efficacy of antimicrobials that could be combined with ceftriaxone to reduce the probability of ceftriaxone resistance emerging and spreading in N. gonorrhoeae.
Methods And Results:
Broth microdilution was used to determine the minimal inhibitory concentrations (MICs) for a panel of ceftriaxone-resistant (WHO X, Y, Z) and ceftriaxone-susceptible (WHO L, N, P) N. gonorrhoeae WHO reference strains for the following antimicrobials: ceftriaxone, doxycycline, azithromycin, zoliflodacin, fosfomycin, pristinamycin, ramoplanin, gentamicin and NAI-107. The MICs for zoliflodacin and pristinamycin for all strains were lower than or equal to the available breakpoints. A checkerboard assay was used to determine the drug-drug combination effect, which showed either an indifferent or an additive effect for all the combinations tested with ceftriaxone.
Conclusions:
The low MICs of zoliflodacin and pristinamycin for the three ceftriaxone-resistant strains suggest that these antimicrobials could be used as partner drugs with ceftriaxone to reduce the probability of ceftriaxone resistance spreading in areas with a high prevalence of ceftriaxone resistance.
Insights
Ceftriaxone-resistant gonorrhea is a growing problem. Zoliflodacin and pristinamycin show promise as partner drugs with ceftriaxone to combat emerging resistance in Neisseria gonorrhoeae.
Area of Science:
- Microbiology
- Antimicrobial Resistance
- Pharmacology
Background:
- The rise of ceftriaxone-resistant Neisseria gonorrhoeae threatens current treatment strategies.
- Urgent need for effective therapeutic combinations to prevent resistance spread.
Purpose of the Study:
- To evaluate antimicrobials for combination therapy with ceftriaxone.
- To mitigate the emergence and spread of ceftriaxone resistance in N. gonorrhoeae.
Main Methods:
- Broth microdilution determined MICs for resistant and susceptible N. gonorrhoeae strains against various antimicrobials.
- Checkerboard assay assessed drug-drug interaction effects in combinations with ceftriaxone.
Main Results:
- Zoliflodacin and pristinamycin exhibited low MICs for all tested N. gonorrhoeae strains, including ceftriaxone-resistant ones.
- Drug combinations with ceftriaxone demonstrated indifferent or additive effects.
Conclusions:
- Zoliflodacin and pristinamycin are potential partner drugs for ceftriaxone therapy.
- These combinations may reduce ceftriaxone resistance spread, especially in high-prevalence areas.
