Journal Club

Carbamazepine as a Possible Treatment for Neisseria gonorrhoeae

By Zeina Kanafani, MD, MS, FIDSA

Recent years have witnessed a concerning rise in the rates of antimicrobial resistance among Neisseria gonorrhoeae isolates, and new treatment options are needed for this common sexually transmitted pathogen.

Carbamazepine, traditionally used as an antiepileptic agent, was found to block the interaction between gonococcal and human host proteins, and in an ex-vivo model, it could clear gonorrheal infection from primary cervical epithelial cells. In a recent study in Antimicrobial Agents and Chemotherapy, women between the ages of 18 and 55 years were divided into two groups: a test group of 6 women who had been treated with at least 200 mg/day of carbamazepine for at least a month, and a control group of 10 women who had never taken carbamazepine. All participants contributed serum, saliva, and vaginal fluid specimens.

Women in the test group had detectable serum levels of carbamazepine that were commensurate with the total daily dose. Carbamazepine was not detected in the sera of subjects in the control group. With regard to saliva samples, there was a statistically significant positive correlation between mean concentrations of carbamazepine in saliva and in serum in the test group but not in the control group (Pearson r = 0.8229; P = .0443). On the other hand, the positive correlation between concentrations of carbamazepine in vaginal fluid and in serum did not reach statistical significance (Pearson r = 0.7963; P = .0580).

The authors then used an ex vivo model of cervicitis to evaluate the effectiveness of vaginal fluid from women taking carbamazepine in treating a gonorrheal infection of primary cervical epithelial cells. Parallel assays on control tissue cultures with no vaginal fluid were performed for comparison. The use of carbamazepine-containing vaginal fluid at 10% dilution for 24 hours significantly reduced the number of viable N. gonorrhoeae cells recovered from cervical epithelial cells by more than 99.9% (P £ .0196). A similar positive effect was observed at lower concentrations of vaginal fluid at 5% and 3.3%. Vaginal fluid from control subjects also reduced the number of viable gonococci, although the decrease was quite small (£ 20.6%; P £ .0164) with even less effect at the 5% and 3.3% dilutions. When carbamazepine was added to the vaginal fluid of test subjects, a 99.9% reduction in the number of viable N. gonorrhoeae from cervical epithelial cells was again noted.

Finally, carbamazepine did not have a direct effect on the viability of N. gonorrhoeae in the absence of cervical epithelial cells, again pointing to its effect on the interaction between the pathogen and the host cell, rather than a direct bactericidal activity.

The authors conclude that carbamazepine may be an effective therapeutic option for gonococcal infection and encourage clinical trials to further evaluate these results.

(Shewell et al. Antimicrob Agents Chemother. 2023;67(1):e0096822.)