Assessment of the In Vitro of Drug Combinations to Inhibit Growth of Neisseria gonorrhoeae

Background:
Resistance to therapeutic agents continues to evolve in Neisseria gonorrhoeae such that cephalosporins and spectinomycin are the only antimicrobial recommended by the Centers for Disease Control and Prevention for the treatment of uncomplicated gonococcal infection. The dearth of antimicrobial choices for the treatment of gonorrhoeae may be offset by examining drug combinations.

Objective:
Assess the in vitro activity of gentamicin / azithromycin and rifampicin / azithromycin against N. gonorrhoeae.

Method:
99 N. gonorrhoeae isolates with known antimicrobial resistance patterns were tested. Susceptabilities were determined to two-fold dilutions of gentamicin (0 to 32 µg/ml) in combination with azithromycin (0 to 8 µg/ml) in Difco GC medium base supplemented with 1% IsoViatleX. A similar set of plates were prepared with rifampicin (0 to 4 µg/ml) in combination with azithromycin (0 to 8 µg/ml). The plates were inoculated with 104 CFU of N. gonorrhoeae and incubated at 36.5oC under 5% CO2. The minimum inhibitory concentration (MIC) of the drug combination was determined after 20 to 24 hours incubation.

Result:
A combination MIC of 4 µg/ml of gentamicin and 2 µg/ml of azithromycin was required to inhibit all of the tested isolates. In contrast, 11 isolates were not inhibited by the combination of 4 µg/ml of rifampicin and 4 µg/ml of azithromycin.

Conclusion:
The combination of gentamicin / azithromycin was effective in restricting the growth of N. gonorrhoeae. This probaly was due to an additive effect as there was a slight decrease in the MIC when these drugs were used in combination. The lack of such an observation for rifampicin / azithromycin suggested that both drugs acted independent of each other.

Implications:
These data indicate that certain drug combinations can inhibit in vitro growth of N. gonorrhoeae in vitro but their applicability for treatment of uncomplicated gonorrhea are limited by the lack of clinical correlation to such therapeutic combinations.