In vitro synergy testing of novel antimicrobial combination therapies against Neisseria gonorrhoeae.
BACKGROUND
Antimicrobial-resistant Neisseria gonorrhoeae is a major public health threat. Current CDC treatment guidelines for uncomplicated gonorrhoea recommend only ceftriaxone plus either azithromycin or doxycycline. Additional treatment options are needed.


METHODS
We used antibiotic gradient synergy testing (the Etest) to evaluate antimicrobial combinations that included a third-generation cephalosporin (cefixime or ceftriaxone) plus azithromycin, doxycycline, gentamicin, rifampicin or fosfomycin. We tested each combination against 28 clinical N. gonorrhoeae isolates and four control strains of varying susceptibility profiles, and compared the results with those obtained using combination antimicrobial testing using agar dilution. We calculated the fractional inhibitory concentration index (FICI) for each combination to determine synergy, the results being interpreted as follows: FICI ≤ 0.5 = synergy; FICI > 4.0 = antagonism; and FICI > 0.5-4 = indifference.


RESULTS
The combinations of a third-generation cephalosporin plus azithromycin, doxycycline, rifampicin, gentamicin or fosfomycin produced FICIs of indifference. The Etest and agar dilution methods produced comparable results.


CONCLUSIONS
Combinations of ceftriaxone plus rifampicin, gentamicin or fosfomycin may warrant further clinical investigation as treatments for gonorrhoea. Using the Etest for synergy testing is a viable method that has practical advantages over agar dilution.
Department of Medicine, Division of Allergy and Infectious Disease, University of Washington, Seattle, WA, USA Public Health - Seattle & King County HIV/STD Program, Seattle, WA, USA lbarbee@u.washington.edu.
Lindley A
LA
Barbee
Neisseria Reference Laboratory, University of Washington, Seattle, WA, USA Department of Global Health, University of Washington, Seattle, WA, USA Center for AIDS and STD, University of Washington, Seattle, WA, USA.
Olusegun O
OO
Soge
Department of Medicine, Division of Allergy and Infectious Disease, University of Washington, Seattle, WA, USA Neisseria Reference Laboratory, University of Washington, Seattle, WA, USA Department of Global Health, University of Washington, Seattle, WA, USA Center for AIDS and STD, University of Washington, Seattle, WA, USA.
King K
KK
Holmes
Department of Medicine, Division of Allergy and Infectious Disease, University of Washington, Seattle, WA, USA Public Health - Seattle & King County HIV/STD Program, Seattle, WA, USA Center for AIDS and STD, University of Washington, Seattle, WA, USA.
Matthew R
MR
Golden
D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use; D004347:Drug Interactions; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006069:Gonorrhea / Q000188:drug therapy / Q000382:microbiology*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents
antimicrobial resistance; novel therapies; sexually transmitted diseases